Antibodies targeting L1CAM and uses thereof

Abstract

Advanced solid tumors remain largely incurable due to the emergence of tumor subclones. These tumor subclones, called metastatic stem cells (MetSCs), are capable of self-renewal, slow cell cycle, tumor relapse, and therapy resistance. The cell adhesion molecule L1CAM has been identified as a key target specifically on MetSCs. The presently disclosed subject matter provides antibodies or antigen-binding fragments thereof that bind to L1CAM, and methods of using such antibodies or antigen-binding fragments. The presently disclosed subject matter further provides immunoconjugates comprising anti-L1CAM antibodies or antigen-binding fragments thereof, and methods of using such immunoconjugates.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63 / 478,829, filed January 6, 2023, the contents of which are incorporated herein by reference in their entirety and to which priority is claimed.

[0002] Sequence Listing This application contains a Sequence Listing, which has been submitted herewith and is incorporated by reference in its entirety. The .xml copy in question, created on December 19, 2023, is named 0727341531.xml and is 290,581 bytes in size.

[0003] The subject matter disclosed herein relates to antibodies that bind to L1CAM, immunoconjugates comprising such antibodies, and methods of using such antibodies and immunoconjugates. [Background technology]

[0004] Advanced solid tumors remain largely incurable due to the emergence of tumor subclones. These tumor subclones, termed metastatic stem cells (MetSCs), are capable of self-renewal, slow cell cycling, tumor relapse, and therapy resistance. The cell adhesion molecule L1CAM has been identified as a key target specifically on MetSCs. L1CAM expression is crucial in multiple solid tumors, including colorectal, lung, breast, ovarian, pancreatic, prostate, and hepatobiliary cancers. + MetSCs are enriched after therapy and regenerate more aggressive metastatic cancers, which are a major cause of cancer mortality. High L1CAM expression in tumors is almost universally associated with poor prognosis.

[0005] L1CAM is a key marker and mediator of quiescent, chemoresistant, stem-like metastatic regenerating cells. Consequently, L1CAM is an attractive target for the treatment of advanced solid tumors. Furthermore, L1CAM is important for the persistence of multiple solid tumors, including the three types that most significantly cause cancer deaths (e.g., lung, breast, and colorectal cancer), in multiple metastatic organ sites such as bone, lung, liver, and brain. L1CAM is important for the proliferation of invasive cancer cells shortly after newly disseminated target organs and indolent cancer cells emerging from dormancy. Therefore, new therapeutic approaches are needed to target this dependency of metastatic stem cells and treat advanced solid tumors. Summary of the Invention

[0006] The presently disclosed subject matter provides antibodies or antigen-binding fragments thereof that specifically bind to L1CAM, immunoconjugates comprising such antibodies, and methods of using the antibodies or antigen-binding fragments thereof.

[0007] The presently disclosed subject matter includes an anti-L1CAM antibody or antigen-binding fragment thereof, (a) a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 2 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 3 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 4 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 5 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 6 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 7 or a conservative modification thereof; (b) a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof; (c) a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof; (d) a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 35 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 36 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 37 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 38 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 39 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 40 or a conservative modification thereof; (e) a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 43 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 44 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 45 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 46 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 47 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 48 or a conservative modification thereof; (f) a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 43 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 44 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 45 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 51 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 52 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 40 or a conservative modification thereof; (g) a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 54 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 55 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 56 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 57 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 58 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 59 or a conservative modification thereof; (h) a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 62 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 63 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 64 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 65 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 58 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 66 or a conservative modification thereof; (i) a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 69 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 71 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 72 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 73 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 74 or a conservative modification thereof; (j) a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 81 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 83 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 84 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 85 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 86 or a conservative modification thereof; (k) a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 93 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 94 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 95 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 96 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 97 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 98 or a conservative modification thereof; (l) a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 105 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 106 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 107 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 108 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 39 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 109 or a conservative modification thereof; or (m) Provided is an anti-L1CAM antibody or antigen-binding fragment thereof, comprising a heavy chain variable region comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 116 or a conservative modification thereof, CDR2 having the amino acid sequence set forth in SEQ ID NO: 117 or a conservative modification thereof, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 118 or a conservative modification thereof, and a light chain variable region comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 119 or a conservative modification thereof, CDR2 having the amino acid sequence set forth in SEQ ID NO: 120, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 121 or a conservative modification thereof.

[0008] In certain embodiments, (a) the heavy chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 2, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 3, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 4, and the light chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 5, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 6, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 7; or (b) the heavy chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14, and the light chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17; or (c) the heavy chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26, and the light chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17; or (d) the heavy chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 35, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 36, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 37, and the light chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 38, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 39, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 40v; or (e) the heavy chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 43, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 44, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 45, and the light chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 46, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 47, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 48; or (f) the heavy chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 43, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 44, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 45, and the light chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 51, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 52, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 40; or (g) the heavy chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 54, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 55, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 56, and the light chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 57, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 58, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 59; or (h) the heavy chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 62, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 63, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 64, and the light chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 65, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 58, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 66; or (i) the heavy chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 69, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 71, and the light chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 72, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 73, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 74; or (j) the heavy chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 81, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 83, and the light chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 84, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 85, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 86; or (k) the heavy chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 93, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 94, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 95, and the light chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 96, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 97, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 98; or (l) the heavy chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 105, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 106, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 107, and the light chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 108, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 39, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 109; or (m) The heavy chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 116, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 117, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 118, and the light chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 119, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 120, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 121.

[0009] In certain embodiments, (a) the heavy chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 2, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 3, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 4, and the light chain variable region comprising CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 5, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 6, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 7; or (b) the heavy chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14, and the light chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17; or (c) The heavy chain variable region comprises CDR1 having the amino acid sequence set forth in SEQ ID NO: 69, CDR2 having the amino acid sequence set forth in SEQ ID NO: 70, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 71, and the light chain variable region comprises CDR1 having the amino acid sequence set forth in SEQ ID NO: 72, CDR2 having the amino acid sequence set forth in SEQ ID NO: 73, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 74.

[0010] In certain embodiments, the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 2, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 3, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 4, and the light chain variable region comprising CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 5, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 6, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 7.

[0011] In certain embodiments, the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14, and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17.

[0012] In certain embodiments, the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 69, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 71, and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 72, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 73, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 74.

[0013] In certain embodiments, the anti-L1CAM antibody or antigen-binding fragment thereof is (a) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% homologous or identical to the amino acid sequence set forth in SEQ ID NO:8, SEQ ID NO:18, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:33, SEQ ID NO:41, SEQ ID NO:49, SEQ ID NO:60, SEQ ID NO:67, SEQ ID NO:75, SEQ ID NO:87, SEQ ID NO:99, SEQ ID NO:110, SEQ ID NO:122, SEQ ID NO:128, SEQ ID NO:130, SEQ ID NO:134, or SEQ ID NO:135; or (b) comprises a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% homologous or identical to the amino acid sequence set forth in SEQ ID NO:9, SEQ ID NO:19, SEQ ID NO:23, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:42, SEQ ID NO:50, SEQ ID NO:53, SEQ ID NO:61, SEQ ID NO:68, SEQ ID NO:76, SEQ ID NO:88, SEQ ID NO:100, SEQ ID NO:111, SEQ ID NO:123, SEQ ID NO:129, SEQ ID NO:131, SEQ ID NO:132, or SEQ ID NO:133.

[0014] In certain embodiments, the anti-L1CAM antibody or antigen-binding fragment thereof is (a) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:8, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:9; (b) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 18, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 19; (c) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 22, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 23; (d) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:24, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:23; (e) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:25, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:23; (f) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:27, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:23; (g) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:28, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:23; (h) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:29, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:23; (i) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 22, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 30; (j) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:24, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:30; (k) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 25, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 30; (l) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 27, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 30; (m) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:28, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:30; (n) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 29, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 30; (o) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 22, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 31; (p) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 24, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 31; (q) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 25, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 31; (r) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:27, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:31; (s) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 28, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 31; (t) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:29, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:31; (u) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 22, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 32; (v) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:24, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:32; (w) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:25, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:32; (x) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 27, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 32; (y) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 28, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 32; (z) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:29, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:32; (aa) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 22, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 19; (ab) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 24, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 19; (ac) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 25, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 19; (ad) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 27, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 19; (ae) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:28, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:19; (af) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:29, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:19; (ag) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 33, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 34; (ah) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 41, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 42; (ai) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 49, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 50; (aj) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 49, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 53; (ak) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 60, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 61; (a1) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 67, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 68; (am) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 75, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 76; (an) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 87, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 88; (ao) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 99, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 100; (ap) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 110, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 111; (aq) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 122, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 123; (ar) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 128, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 129; (as) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 130, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 131; (at) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 130, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 132; (au) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 130, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 133; (av) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 134, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 131; (aw) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 134, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 132; (ax) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 134, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 133; (ay) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 135, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 131; (az) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 135, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 132; (ba) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 135, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 133; and (bb) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 135, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 136.

[0015] In certain embodiments, (a) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 8 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 9; or (b) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 18 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 19; or (c) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 22 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 23; or (d) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 24 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 23; or (e) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 25 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 23; or (f) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 27 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 23; or (g) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 28 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 23; or (h) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 29 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 23; or (i) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 22 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 30; or (j) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 24 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 30; or (k) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 25 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 30; or (l) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 27 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 30; or (m) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 28 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 30; or (n) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 29 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 30; or (o) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 22 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 31; or (p) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 24 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 31; or (q) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 25 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 31; or (r) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 27 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 31; or (s) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 28 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 31; or (t) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 29 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 31; or (u) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 22 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 32; or (v) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 24 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 32; or (w) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 25 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 32; or (x) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 27 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 32; or (y) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 28 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 32; or (z) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 29 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 32; or (aa) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 22 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 19; or (ab) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 24 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 19; or (ac) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 25 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 19; or (ad) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 27 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 19; or (ae) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 28 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 19; or (af) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 29 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 19; or (ag) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 33 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 34; or (ah) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 41 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 42; or (ai) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 49 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 50; or (aj) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 49 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 53; or (ak) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 60 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 61; or (a1) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 67 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 68; or (am) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 75 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 76; or (an) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 87 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 88; or (ao) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 99 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 100; or (ap) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 110 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 111; or (aq) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 122 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 123; or (ar) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 128 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 129; or (as) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 130 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 131; or (at) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 130 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 132; or (au) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 130 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 133; or (av) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 134 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 131; or (aw) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 134 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 132; or (ax) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 134 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 133; or (ay) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 135 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 131; or (az) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 135 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 132; or (ba) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 135 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 133; or (bb) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 135, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 136.

[0016] In certain embodiments, the antibody comprises a heavy chain constant region and / or a light chain constant region. (a) the heavy chain constant region comprises an amino acid sequence that is about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% identical to the amino acid sequence set forth in SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, or SEQ ID NO: 147; and / or (b) the light chain constant region comprises an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 148.

[0017] In certain embodiments, (a) the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, or SEQ ID NO: 147; and / or (b) the light chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 148.

[0018] In certain embodiments, the antibody comprises a human variable region framework region. In certain embodiments, the antibody or antigen-binding fragment thereof is fully human or an antigen-binding fragment thereof. In certain embodiments, the antibody or antigen-binding fragment thereof is a chimeric antibody or antigen-binding fragment thereof. In certain embodiments, the antibody or antigen-binding fragment thereof is a humanized antibody or antigen-binding fragment thereof. In certain embodiments, the antigen-binding fragment is a Fab, Fab', F(ab')2, variable fragment (Fv), or single-chain variable region (scFv). In certain embodiments, the antigen-binding fragment is an scFv.

[0019] The subject matter disclosed herein also includes (a) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 8, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 9; (b) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 18, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 19; (c) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 22, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 23; (d) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 24, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 23; (e) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 25, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 23; (f) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 27, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 23; (g) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 28, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 23; (h) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 29, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 23; (i) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 22, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 30; (j) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 24, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 30; (k) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 25, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 30; (l) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 27, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 30; (m) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 28, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 30; (n) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 29, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 30; (o) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 22, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 31; (p) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 24, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 31; (q) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 25, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 31; (r) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 27, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 31; (s) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 28, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 31; (t) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 29, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 31; (u) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 22, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 32; (v) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 24, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 32; (w) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 25, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 32; (x) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 27, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 32; (y) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 28, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 32; (z) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 29, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 32; (aa) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 22, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 19; (ab) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 24, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 19; (ac) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 25, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 19; (ad) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 27, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 19; (ae) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 28, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 19; (af) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 29, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 19; (ag) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 33, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 34; (ah) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 41, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 42; (ai) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 49, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 50; (aj) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 49, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 53; (ak) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 60, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 61; (a1) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 67, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 68; (am) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 75, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 76; (an) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 87, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 88; (ao) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 99, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 100; (ap) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 110, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 111; (aq) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 122, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 123; (ar) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 128, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 129; (as) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 130, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 131; (at) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 130, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 132; (au) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 130, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 133; (av) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 134, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 131; (aw) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 134, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 132; (ax) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 134, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 133; (ay) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 135, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 131; (az) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 135, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 132; (ba) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 135, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 133; or (bb) Also provided is an anti-L1CAM antibody or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 135, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 136.

[0020] The subject matter disclosed herein also includes (a) a single-chain variable region (scFv) comprising an amino acid sequence that is about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% identical to SEQ ID NO: 77 or SEQ ID NO: 78; (b) a single-chain variable region (scFv) comprising an amino acid sequence that is about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% identical to SEQ ID NO: 89 or SEQ ID NO: 90; (c) a single-chain variable region (scFv) comprising an amino acid sequence that is about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% identical to SEQ ID NO: 101 or SEQ ID NO: 102; (d) a single chain variable region (scFv) comprising an amino acid sequence that is about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% identical to SEQ ID NO: 112 or SEQ ID NO: 113; or (e) Also provided is an anti-L1CAM antibody or antigen-binding fragment thereof comprising a single-chain variable region (scFv) comprising an amino acid sequence that is about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% identical to SEQ ID NO: 124 or SEQ ID NO: 125.

[0021] In certain embodiments, (a) the scFv comprises the amino acid sequence set forth in SEQ ID NO: 77 or SEQ ID NO: 78; (b) the scFv comprises the amino acid sequence set forth in SEQ ID NO: 89 or SEQ ID NO: 90; (c) the scFv comprises the amino acid sequence set forth in SEQ ID NO: 101 or SEQ ID NO: 102; (d) the scFv comprises the amino acid sequence set forth in SEQ ID NO: 112 or SEQ ID NO: 113; or (e) The scFv comprises the amino acid sequence set forth in SEQ ID NO: 124 or SEQ ID NO: 125.

[0022] The subject matter disclosed in this specification further provides an anti-L1CAM antibody or antigen-binding fragment thereof, comprising a heavy chain variable region comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 2, CDR2 having the amino acid sequence set forth in SEQ ID NO: 3, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 4, and a light chain variable region comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 5, CDR2 having the amino acid sequence set forth in SEQ ID NO: 6, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 7.

[0023] The subject matter disclosed in this specification also provides an anti-L1CAM antibody or antigen-binding fragment thereof, comprising a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17.

[0024] The subject matter disclosed in this specification also provides an anti-L1CAM antibody or antigen-binding fragment thereof, comprising a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 69, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 71, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 72, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 73, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 74.

[0025] The subject matter disclosed in this specification also provides an anti-L1CAM antibody or antigen-binding fragment thereof, comprising a heavy chain variable region comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 81, CDR2 having the amino acid sequence set forth in SEQ ID NO: 82, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 83, and a light chain variable region comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 84, CDR2 having the amino acid sequence set forth in SEQ ID NO: 85, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 86.

[0026] The subject matter disclosed in this specification also provides an anti-L1CAM antibody or antigen-binding fragment thereof, comprising a heavy chain variable region comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 93, CDR2 having the amino acid sequence set forth in SEQ ID NO: 94, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 95, and a light chain variable region comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 96, CDR2 having the amino acid sequence set forth in SEQ ID NO: 97, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 98.

[0027] The subject matter disclosed herein also provides an anti-L1CAM antibody or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:8, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:9.

[0028] The subject matter disclosed herein also provides an anti-L1CAM antibody or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 18, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 19.

[0029] The subject matter disclosed herein also provides an anti-L1CAM antibody or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 75, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 76.

[0030] The subject matter disclosed herein also provides an anti-L1CAM antibody or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 87, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 88.

[0031] The subject matter disclosed herein also provides an anti-L1CAM antibody or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 99, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 100.

[0032] The presently disclosed subject matter also provides an anti-L1CAM antibody or antigen-binding fragment thereof, comprising an scFv comprising the amino acid sequence set forth in SEQ ID NO:77 or SEQ ID NO:78.

[0033] The presently disclosed subject matter also provides an anti-L1CAM antibody or antigen-binding fragment thereof, comprising an scFv comprising the amino acid sequence set forth in SEQ ID NO:89 or SEQ ID NO:90.

[0034] The presently disclosed subject matter also provides an anti-L1CAM antibody or antigen-binding fragment thereof, comprising an scFv comprising the amino acid sequence set forth in SEQ ID NO:101 or SEQ ID NO:102.

[0035] In certain embodiments, the presently disclosed subject matter provides an antibody or antigen-binding fragment thereof that cross-competes for binding to or binds to the same epitope region on L1CAM as an anti-L1CAM antibody or antigen-binding fragment thereof disclosed herein.

[0036] The presently disclosed subject matter further provides an immunoconjugate comprising the anti-L1CAM antibody or antigen-binding fragment thereof disclosed herein. In certain embodiments, the anti-L1CAM antibody or antigen-binding fragment thereof is linked to a therapeutic agent. In certain embodiments, the therapeutic agent is a drug, a cytotoxin, or a radioisotope. In certain embodiments, the therapeutic agent is a compound selected from the following classes of compounds: dolastatins, maytansinoids, duocarmycins, anthracyclines, camptothecins, and amatoxins. In certain embodiments, the therapeutic agent is selected from the group consisting of monomethyl auristatin E, ABZ038, duocarmycin™, PNU159682, SN38, and α-amanitin. In certain embodiments, the therapeutic agent is PNU159682.

[0037] In certain embodiments, the immunoconjugate comprises a linker. In certain embodiments, the linker is a cleavable linker or a non-cleavable linker. In certain embodiments, the immunoconjugate comprises a molecule of the following formula: [ka]

[0038] In certain embodiments, the immunoconjugate comprises a molecule of the following formula: [ka]

[0039] The presently disclosed subject matter further provides multispecific molecules comprising an anti-L1CAM antibody or antigen-binding fragment thereof disclosed herein linked to one or more functional moieties, in certain embodiments, the one or more functional moieties have a binding specificity that is different from that of the anti-L1CAM antibody or antigen-binding fragment thereof.

[0040] The presently disclosed subject matter also provides compositions comprising the anti-L1CAM antibody or antigen-binding fragment thereof, immunoconjugate, or multispecific molecule disclosed herein. In certain embodiments, the composition is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier.

[0041] The presently disclosed subject matter provides nucleic acids encoding the anti-L1CAM antibody or antigen-binding fragment thereof, the heavy chain variable region of the anti-L1CAM antibody or antigen-binding fragment thereof, and / or the light chain variable region of the anti-L1CAM antibody or antigen-binding fragment thereof disclosed herein. In certain embodiments, the presently disclosed subject matter provides vectors or host cells comprising the nucleic acids disclosed herein.

[0042] The presently disclosed subject matter further provides methods for detecting L1CAM in whole cells, tissues, or blood samples. In certain embodiments, the methods include contacting cells, tissues, or blood samples with an anti-L1CAM antibody or antigen-binding fragment thereof disclosed herein. In certain embodiments, the anti-L1CAM antibody or antigen-binding fragment thereof comprises a detectable label. In certain embodiments, the methods include determining the amount of labeled antibody or antigen-binding fragment thereof bound to the cells, tissues, or blood sample by measuring the amount of detectable label associated with the cells or tissues, where the amount of bound antibody or antigen-binding fragment thereof indicates the amount of L1CAM in the cells, tissues, or blood sample.

[0043] The presently disclosed subject matter provides methods for treating or ameliorating an L1CAM-associated disease or disorder in a subject, reducing tumor burden in a subject, treating and / or preventing a tumor in a subject, and increasing or prolonging survival of a tumor-bearing subject. In certain embodiments, the method comprises administering to the subject an anti-L1CAM antibody or antigen-binding fragment thereof, immunoconjugate, multispecific molecule, or composition disclosed herein.

[0044] In certain embodiments, the disease or disorder is a tumor. In certain embodiments, the method reduces the number of tumor cells, reduces tumor size, and / or eradicates a tumor in a subject. In certain embodiments, the method reduces or eradicates a tumor burden in a subject. In certain embodiments, the tumor is a cancer. In certain embodiments, the tumor is a metastatic cancer. In certain embodiments, the metastatic cancer is an advanced metastatic cancer. In certain embodiments, the subject is a human.

[0045] The presently disclosed subject matter further provides kits for treating or ameliorating a disease or disorder in a subject, reducing tumor burden in a subject, treating and / or preventing a tumor in a subject, and / or increasing or prolonging survival of a subject with a tumor, the kit comprising an anti-L1CAM antibody or antigen-binding fragment thereof, immunoconjugate, multispecific molecule, or composition disclosed herein. In certain embodiments, the kit further comprises written instructions for using the antibody or antigen-binding fragment thereof, immunoconjugate, multispecific molecule, or composition disclosed herein.

[0046] The following detailed description, given by way of example and not intended to limit the invention to the particular embodiments described, may be understood in conjunction with the accompanying drawings, in which: [Brief explanation of the drawings]

[0047] [Figure 1] Figure 1A shows the effect of L1CAM on metastatic growth. This shows that L1CAM mediates cancer cell spread. Figure 1B shows the effect of L1CAM on metastatic growth. This shows that L1CAM expression is associated with poor survival in CRC. Figure 1C shows the effect of L1CAM on metastatic growth. This shows that doxycycline-induced L1CAM knockdown after intracardiac injection of lung adenocarcinoma cells reduces metastatic growth. Figure 1D shows the effect of L1CAM on metastatic growth. This shows that L1CAM knockdown reduces YAP nuclear localization in H2030-BrM lung adenocarcinoma cells spreading on the vascular basement membrane. Figure 1E shows the effect of L1CAM on metastatic growth. This shows that the reduction in brain metastasis by L1CAM knockdown is rescued by the active YAP5SA mutant, but not the inactive YAPS94A mutant. Figure 1F shows the effect of L1CAM on metastatic growth. A representative model of metastatic growth is shown. L1CAM amplifies integrin-ILK signaling and induces the YAP transcriptional program for metastatic colonization. [Figure 2] Figure 2A shows L1CAM expression in human lung cancer and colorectal cancer. L1CAM enrichment in post-therapy residual disease in lung is shown. Figure 2B shows L1CAM expression in human lung cancer and colorectal cancer. L1CAM enrichment in post-therapy residual disease in colorectal cancer is shown. Figure 2C shows L1CAM expression in human lung cancer and colorectal cancer. L1CAM+ cells express low levels of the proliferation marker Ki67. [Figure 3]Figure 3A shows CRC organoids and the different L1CAM+ populations that drive metastatic regeneration. Figure 3B shows CRC organoids and the different L1CAM+ populations that drive metastatic regeneration. Figure 3C shows L1CAM+ cells FACS sorted from resected CRC liver metastases of patients regenerate xenograft tumors more efficiently than L1CAM- cells. Figure 3D shows CRC organoids and the different L1CAM+ populations that drive metastatic regeneration. Figure 3D shows single-cell mRNA sequencing of primary tumor / liver metastasis CRC patient-derived organoids with differential abundance of LGR5+ tumor-initiating cells and L1CAM+ metastatic stem cells. Figure 3E shows the distinct L1CAM+ populations that drive CRC organoids and metastatic regeneration. Single-cell mRNA sequencing of primary tumor / liver metastasis CRC patient-derived organoids shows differential abundance of LGR5+ tumor-initiating cells and L1CAM+ metastatic stem cells. [Figure 4] L1CAM+ cells in normal and metastatic regeneration are shown. [Figure 5-1]Figure 5A shows the plasticity of the L1CAM+ MetSC phenotype. This figure demonstrates that L1CAM expression is dynamically regulated during organoid growth. L1CAM immunohistochemical staining is restricted to cells at the periphery, and there is an overall decrease in L1CAM expression with increasing organoid size. Figure 5B shows the plasticity of the L1CAM+ MetSC phenotype. L1CAM is induced by dissociation of normal, primary, and metastatic human CRC organoids. Figure 5C shows the plasticity of the L1CAM+ MetSC phenotype. A time course of regeneration of organoids derived from L1CAMhigh (left) or L1CAMlow (right) organoids sorted from 21-day MSK107Li (top) or MSK121Li (bottom) organoids is shown. Figure 5D shows the plasticity of the L1CAM+ MetSC phenotype. This figure demonstrates the dynamic induction of the L1CAMhigh phenotype by a subset of pre-existing L1CAMlow cells. The percentages of tdTomato- and GFP-expressing cells are shown. Figure 5E shows the plasticity of the L1CAM+ MetSC phenotype. Figure 5F shows the distribution of cells derived from tdTomato+GFP-L1CAMhigh and tdTomato-GFP+L1CAMlow precursors. Figure 5G shows the plasticity of the L1CAM+ MetSC phenotype. Figure 5H shows the plasticity of the L1CAM+ MetSC phenotype. Figure 5I ...I shows the plasticity of the L1CAM+ MetSC phenotype. Figure 5I shows the plasticity of the L1CAM+ MetSC phenotype. Figure 5I shows the plasticity of the L1CAM+ MetSC phenotype. Figure 5I shows the plasticity of the L1CAM+ MetSC phenotype. Figure 5I shows the plasticity of the L1CAM+ MetSC phenotype. Figure 5I shows the plasticity of the L1CAM+ MetSC phenotype. Figure 5J shows the plasticity of the L1CAM+ MetSC phenotype, demonstrating that the combination of L1CAM inhibition with chemotherapy impairs tumor growth in vivo to a greater extent than chemotherapy alone. [Figure 5-2] Same as above. [Figure 6] An overview of the screening funnel and hits for hybridoma supernatants is shown. The steps of the screening funnel are shown in order on the left. For each step, the method used, selection criteria, and number of hits for wild-type mice (Balb / c&A / J) and transgenic mice (AlivaMab®) are shown. [Figure 7] Figure 1 shows the internalization of L1CAM lead candidate mAbs. The Fab-ZAP assay was used to determine the internalization potency of L1CAM lead candidate mAbs in HEK293T cells overexpressing human L1CAM. L1CAM mAbs and mouse IgG1 isotype controls were preincubated at various concentrations with saporin-conjugated Fab fragments that bind to mouse Fc. After 5 days, cell viability was measured and plotted against mAb concentration. [Figure 8] 1 shows KD determination by BLI of humanized variants. [Figure 9] 1 shows binding of humanized variants of the antibodies disclosed herein to cells expressing L1CAM by FACS analysis. [Figure 10] The interaction between human L1CAM (huL1CAM) and TDI-Y-004 is shown in SEQ ID NO: 317 in Figure 10. [Figure 11]Figure 11A shows a 3D rendering of the interaction between human L1CAM (huL1CAM) and TDI-Y-004. The PDB structure of huL1CAM was generated using Swissmodel software, and the epitope site was identified. The identified amino acids correspond to huL1CAM positions 155-169 (KQDERVTMGQNGNLY, SEQ ID NO: 149), 209-214 (SMIDRK, ​​SEQ ID NO: 150), and 276-286 (KVGEEDDGEYR, SEQ ID NO: 151). A ribbon representation of the front view is shown. Figure 11B shows a 3D rendering of the interaction between human L1CAM (huL1CAM) and TDI-Y-004. The PDB structure of huL1CAM was generated using Swissmodel software, and the epitope site was identified. The identified amino acids correspond to positions 155-169 (KQDERVTMGQNGNLY, SEQ ID NO: 149), 209-214 (SMIDRK, ​​SEQ ID NO: 150), and 276-286 (KVGEEDDGEYR, SEQ ID NO: 151) of huL1CAM. A rear view is shown. Figure 11C shows a 3D rendering of the interaction between human L1CAM (huL1CAM) and TDI-Y-004. The PDB structure of huL1CAM was generated using Swissmodel software, and the epitope sites were identified. The identified amino acids correspond to positions 155-169 (KQDERVTMGQNGNLY, SEQ ID NO: 149), 209-214 (SMIDRK, ​​SEQ ID NO: 150), and 276-286 (KVGEEDDGEYR, SEQ ID NO: 151) of huL1CAM. A first side view is shown. Figure 11D shows a 3D rendering of the interaction between human L1CAM (huL1CAM) and TDI-Y-004. The PDB structure of huL1CAM was generated using Swissmodel software, and the epitope site was identified. The identified amino acids correspond to huL1CAM residues 155-169 (KQDERVTMGQNGNLY, SEQ ID NO: 149), 209-214 (SMIDRK, ​​SEQ ID NO: 150), and 276-286 (KVGEEDDGEYR, SEQ ID NO: 151). A second side view is shown. Figure 11E shows a 3D rendering of the interaction between human L1CAM (huL1CAM) and TDI-Y-004.The PDB structure of huL1CAM was generated using Swissmodel software, and the epitope site was identified. The identified amino acids correspond to 155-169 (KQDERVTMGQNGNLY, SEQ ID NO: 149), 209-214 (SMIDRK, ​​SEQ ID NO: 150), and 276-286 (KVGEEDDGEYR, SEQ ID NO: 151) of huL1CAM. A top view is shown. [Figure 12] SEQ ID NO: 318 is shown in Figure 10, which shows the interaction between human L1CAM (huL1CAM) and TDI-Y-005. [Figure 13]Figure 13A shows a 3D rendering of the interaction between human L1CAM (huL1CAM) and TDI-Y-005. The PDB structure of huL1CAM was generated using Swissmodel software, and the epitope site was identified. The identified amino acids correspond to 622-639 (KYDIEFEDKEMAPEKWYS, SEQ ID NO: 152) and 714-730 (RWMDWNAPQVQYRVQWR, SEQ ID NO: 153) of huL1CAM. A ribbon representation of the front view is shown. Figure 13B shows a 3D rendering of the interaction between human L1CAM (huL1CAM) and TDI-Y-005. The PDB structure of huL1CAM was generated using Swissmodel software, and the epitope site was identified. The identified amino acids correspond to positions 622-639 (KYDIEFEDKEMAPEKWYS, SEQ ID NO: 152) and 714-730 (RWMDWNAPQVQYRVQWR, SEQ ID NO: 153) of huL1CAM. A rear view is shown. Figure 13C shows a 3D rendering of the interaction between human L1CAM (huL1CAM) and TDI-Y-005. The PDB structure of huL1CAM was generated using Swissmodel software, and the epitope site was identified. The identified amino acids correspond to positions 622-639 (KYDIEFEDKEMAPEKWYS, SEQ ID NO: 152) and 714-730 (RWMDWNAPQVQYRVQWR, SEQ ID NO: 153) of huL1CAM. A first side view is shown. Figure 13D shows a 3D rendering of the interaction between human L1CAM (huL1CAM) and TDI-Y-005. The PDB structure of huL1CAM was generated using Swissmodel software, and the epitope site was identified. The identified amino acids correspond to 622-639 (KYDIEFEDKEMAPEKWYS, SEQ ID NO: 152) and 714-730 (RWMDWNAPQVQYRVQWR, SEQ ID NO: 153) of huL1CAM. A second side view is shown. Figure 13E shows a 3D rendering of the interaction between human L1CAM (huL1CAM) and TDI-Y-005. The PDB structure of huL1CAM was generated using Swissmodel software, and the epitope site was identified.The identified amino acids correspond to 622-639 (KYDIEFEDKEMAPEKWYS, SEQ ID NO: 152) and 714-730 (RWMDWNAPQVQYRVQWR, SEQ ID NO: 153) of huL1CAM. [Figure 14-1] Figure 14A shows the binding of TDI-Y-004 and TDI-Y-005 to overexpressed and endogenous L1CAM on cells. HEK293T cells overexpressing L1CAM are shown stained with TDI-Y-004 and TDI-Y-005 at the indicated concentrations. MFI values ​​are normalized to the secondary antibody-only control (MFI ratio). [Figure 14-2] Figure 14B shows the binding of TDI-Y-004 and TDI-Y-005 to overexpressed and endogenous L1CAM on cells. Shown are MCF-7 cells overexpressing L1CAM stained with TDI-Y-004 and TDI-Y-005 at the indicated concentrations. MFI values ​​are normalized to the secondary antibody-only control (MFI ratio). [Figure 14-3] Figure 14C shows the binding of TDI-Y-004 and TDI-Y-005 to overexpressed and endogenous L1CAM on cells. MDA-MB-231 cells expressing endogenous L1CAM were stained with TDI-Y-004 and TDI-Y-005 at the indicated concentrations. MFI values ​​were normalized to the secondary antibody-only control (MFI ratio). [Figure 15] Figure 1 shows the ThioBridge® ADC platform. The interchain disulfide bonds between the heavy and light chains and the hinge region of IgG are reduced to generate pairs of cysteine ​​residues with free thiols, which serve as acceptor sites for bis-sulfone-bis-alkylated linking units that covalently bridge the disulfides. A spacer containing a polymer chain is included to increase the hydrophilicity of the ADC. Toxic drugs are conjugated via self-immolative release linkers. [Figure 16-1]Figure 16A shows the linker-payload structures used for conjugation to anti-L1CAM human IgG1 antibodies h14A10, hz143G03 (N61Q), and isotype control antibody hIgG1. ThioBridge® non-cleavable PNU159682 is shown. [Figure 16-2] Figure 16B shows the linker-payload structures used for conjugation to anti-L1CAM human IgG1 antibodies h14A10, hz143G03 (N61Q), and isotype control antibody hIgG1. ThioBridge® "Glu-Val-Cit-PAB" cleavable PNU159682 is shown. [Figure 17-1]

[0023] Figure 1 shows the cytotoxicity of antibody-drug conjugates (ADCs). ADCs with six different toxic payloads conjugated to 143G03, 14A10, and isotype control mouse IgG1 were screened for their killing efficacy in various cell types, as shown. Free drug was included when available. [Figure 17-2] Same as above. [Figure 17-3] Same as above. [Figure 18] Cytotoxicity of TDI-Y-004 and TDI-Y-005 ADCs with PNU-159682 is shown. In addition to the lead mAbs (TDI-Y-004 and TDI-Y-005), ADCs generated with PNU-159682 and a human IgG1 isotype control (hIgG1) with a cleavable (top) or non-cleavable (bottom) linker were added to HEK293T-L1CAM, MCF-7, or MDA-MB-231 cells, as indicated. A killing curve for free PNU-159682 is included for each construct. RLU, relative luciferase units. [Figure 19-1]Figure 19A shows analytical data for antibody-drug conjugates. Deconvoluted LC-MS spectra for the h14A10 ThioBridge®-Glu[-Glu(OH)-Val-Cit-PAB-DMEA-PNU159682]-PEG(24) conjugate (top spectrum) and mAb h14A10 (bottom spectrum) are shown. The amino acid sequence EEEVX is set forth as SEQ ID NO: 319. The amino acid sequence EGGG is set forth as SEQ ID NO: 320. [Figure 19-2] Figure 19B shows analytical data for the antibody-drug conjugate. Hydrophobic interaction chromatograms (A = 280 nm) for h14A10 ThioBridge®-Glu[-Glu(OH)-Val-Cit-PAB-DMEA-PNU159682]-PEG(24) and mAb h13A10 are shown. The amino acid sequence EEEVX is set forth as SEQ ID NO: 319. The amino acid sequence EGGG is set forth as SEQ ID NO: 320. [Figure 19-3] Figure 19C shows analytical data for the antibody-drug conjugate. Size exclusion chromatograms (A = 280 nm) for h14A10 ThioBridge®-Glu[-Glu(OH)-Val-Cit-PAB-DMEA-PNU159682]-PEG(24) and a PBS blank are shown. The amino acid sequence EEEVX is set forth as SEQ ID NO: 319. The amino acid sequence EGGG is set forth as SEQ ID NO: 320. [Figure 19-4]Figure 19D shows analytical data for antibody-drug conjugates. Non-reducing SDS-PAGE analysis of the following samples is shown: (1) Novex Sharp MW marker, (2) mAb h14A10, (3) mAb h14A10 reduced with TCEP (6 equivalents per mAb) at 40°C for 1 hour, (4) h14A10 ThioBridge®-Glu[-Glu(OH)-Val-Cit-PAB-DMEA-PNU159682]-PEG(24), (5) mAb hz143G03(N61Q), (6) mAb reduced with TCEP (6 equivalents per mAb) at 40°C for 1 hour. hz143G03(N61Q), (7) hz143G03(N61Q) ThioBridge®-Glu[-Glu(OH)-Val-Cit-PAB-DMEA-PNU159682]-PEG(24), (8) mAb hIgG1, (9) mAb hIgG1 reduced with TCEP (6 equivalents per mAb) at 40°C for 1 hour, (10) hIgG1 ThioBridge®-Glu[-Glu(OH)-Val-Cit-PAB-DMEA-PNU159682]-PEG(24). The amino acid sequence EEEVX is set forth as SEQ ID NO: 319. The amino acid sequence EGGG is set forth as SEQ ID NO: 320. [Figure 19-5] Figure 19E shows analytical data for antibody-drug conjugates. Size-exclusion chromatograms (A = 495 nm) are shown for h14A10 ThioBridge®-Glu[-Glu(OH)-Val-Cit-PAB-DMEA-PNU159682]-PEG(24) (TDI100-JN006), hz143G03(N61Q) ThioBridge®-Glu[-Glu(OH)-Val-Cit-PAB-DMEA-PNU159682]-PEG(24) (TDI100-JN007), hIgG1 ThioBridge®-Glu[-Glu(OH)-Val-Cit-PAB-DMEA-PNU159682]-PEG(24) (TDI100-JN008), and a PBS blank. The amino acid sequence EEEVX is set forth as SEQ ID NO: 319. The amino acid sequence EGGG is set forth as SEQ ID NO:320. [Figure 19-6]Figure 19F shows analytical data for antibody-drug conjugates. Deconvoluted LC-MS spectra for the h143G03 ThioBridge®-Glu[-Glu(OH)-Val-Cit-PAB-DMEA-PNU159682]-PEG(24) conjugate (top spectrum) and mAb hz143G03(N61Q) (bottom spectrum) are shown. The amino acid sequence EEEVX is set forth as SEQ ID NO: 319. The amino acid sequence EGGG is set forth as SEQ ID NO: 320. [Figure 19-7] Figure 19G shows analytical data for the antibody-drug conjugate. Hydrophobic interaction chromatograms (A = 280 nm) for hz143G03(N61Q) ThioBridge®-Glu[-Glu(OH)-Val-Cit-PAB-DMEA-PNU159682]-PEG(24) and mAb hz143G03(N61Q) are shown. The amino acid sequence EEEVX is set forth as SEQ ID NO: 319. The amino acid sequence EGGG is set forth as SEQ ID NO: 320. [Figure 19-8] Figure 19H shows analytical data for the antibody-drug conjugate. Size exclusion chromatograms (A = 280 nm) for hz143G03(N61Q) ThioBridge-GluEGIu(OH)-Val-Cit-PAB-DMEA-PNU1596821-PEG(24) and a PBS blank are shown. The amino acid sequence EEEVX is set forth as SEQ ID NO: 319. The amino acid sequence EGGG is set forth as SEQ ID NO: 320. [Figure 19-9] Figure 19I shows analytical data for antibody-drug conjugates. Deconvoluted LC-MS spectra for hIgG1 ThioBridge®-Glu[-Glu(OH)-Val-Cit-PAB-DMEA-PNU159682]-PEG(24) conjugate (top spectrum) and mAb hIgG1 (bottom spectrum) are shown. The amino acid sequence EEEVX is set forth as SEQ ID NO: 319. The amino acid sequence EGGG is set forth as SEQ ID NO: 320. [Figure 19-10]Figure 19J shows analytical data for antibody-drug conjugates. Hydrophobic interaction chromatograms (A = 280 nm) for hIgG1 ThioBridge®-Glu[-Glu(OH)-Val-Cit-PAB-DMEA-PNU159682]-PEG(24) and mAb hIgG1 are shown. The amino acid sequence EEEVX is set forth as SEQ ID NO: 319. The amino acid sequence EGGG is set forth as SEQ ID NO: 320. [Figure 19-11] Figure 19K shows analytical data for the antibody-drug conjugate. Size-exclusion chromatograms (A = 280 nm) for hIgG1 ThioBridge-GluEGlu(OH)-Val-Cit-PAB-DMEA-PNU159682]-PEG(24) and a PBS blank are shown. The amino acid sequence EEEVX is set forth as SEQ ID NO: 319. The amino acid sequence EGGG is set forth as SEQ ID NO: 320. [Figure 19-12] Figure 19L shows analytical data for the antibody-drug conjugate. Deconvoluted LC-MS spectra of h14A10 ThioBridge6-Glu(-Gly3-EDA-PNU159682)-PEG(24u) (top spectrum) and mAb h14A10 (bottom spectrum) are shown. The amino acid sequence EEEVX is set forth as SEQ ID NO: 319. The amino acid sequence EGGG is set forth as SEQ ID NO: 320. [Figure 19-13] Figure 19M shows analytical data for antibody-drug conjugates. Hydrophobic interaction chromatograms (A = 280 nm) for h14A10 ThioBridge®-Glu(-Gly3-EDA-PNU159682)-PEG(24u) and mAb h14A10 are shown. The amino acid sequence EEEVX is set forth as SEQ ID NO: 319. The amino acid sequence EGGG is set forth as SEQ ID NO: 320. [Figure 19-14]Figure 19N shows analytical data for the antibody-drug conjugate. Size exclusion chromatograms (A = 280 nm) for h14A10 ThioBridge®-Glu(-Gly3-EDA-PNU159682)-PEG(24u) and a PBS blank are shown. The amino acid sequence EEEVX is set forth as SEQ ID NO: 319. The amino acid sequence EGGG is set forth as SEQ ID NO: 320. [Figure 19-15] FIG. 19O shows analytical data for antibody-drug conjugates. Non-reducing SDS-PAGE analysis of the following samples is shown: (1) Novex Sharp MW marker, (2) mAb h14A10, (3) mAb h14A10 reduced with TCEP (6 equivalents per mAb) at 40°C for 1 hour, (4) h14A10 ThioBridge®-Glu(-Gly3-EDA-PNU159682)-PEG(24u), (5) mAb hz143G03(N61Q), (6) mAb hz143G03(N61Q) reduced with TCEP (6 equivalents per mAb) at 40°C for 1 hour, (7) hz143G03(N61Q) ThioBridge®-Glu(-Gly3-EDA-PNU159682)-PEG(24u), (8) mAb hIgG1, (9) mAb hIgG1 reduced with TCEP (6 equivalents per mAb) at 40°C for 1 hour, (10) hIgG1 ThioBridge®-Glu(-Gly3-EDA-PNU159682)-PEG(24u). The amino acid sequence EEEVX is set forth as SEQ ID NO: 319. The amino acid sequence EGGG is set forth as SEQ ID NO: 320. [Figure 19-16]Figure 19P shows analytical data for antibody-drug conjugates. Size exclusion chromatograms (A = 495 nm) are shown for h14A10 ThioBridge®-Glu(-Gly3-EDA-PNU159682)-PEG(24 u) (TDI100-JN004), h143G03 ThioBridge®-Glu(-Gly3-EDA-PNU159682)-PEG(24 u) (TDI100-JN005), hIgG1 ThioBridge®-Glu(-Gly3-EDA-PNU159682)-PEG(24 u) (TDI100-JN003), and a PBS blank. The amino acid sequence EEEVX is set forth as SEQ ID NO: 319. The amino acid sequence EGGG is set forth as SEQ ID NO: 320. [Figure 19-17] Figure 19Q shows analytical data for the antibody-drug conjugate. Deconvoluted LC-MS spectra of hz143G03(N61Q) ThioBridge®-Glu(-Gly3-EDA-PNU159682)-PEG(24u) conjugate (top spectrum) and mAb hz143G03(N61Q) (bottom spectrum) are shown. The amino acid sequence EEEVX is set forth as SEQ ID NO: 319. The amino acid sequence EGGG is set forth as SEQ ID NO: 320. [Figure 19-18] Figure 19R shows analytical data for antibody-drug conjugates. Hydrophobic interaction chromatograms (A = 280 nm) for hz143G03(N61Q) ThioBridge®-Glu(-Gly3-EDA-PNU159682)-PEG(24u) and mAb hz143G03(N61Q) are shown. The amino acid sequence EEEVX is set forth as SEQ ID NO: 319. The amino acid sequence EGGG is set forth as SEQ ID NO: 320. [Figure 19-19]Figure 19S shows analytical data for the antibody-drug conjugate. Size exclusion chromatograms (A = 280 nm) for hz143G03 (N61Q) ThioBridge®-Glu(-Gly3-EDA-PNU159682)-PEG (24 u) and a PBS blank are shown. The amino acid sequence EEEVX is set forth as SEQ ID NO: 319. The amino acid sequence EGGG is set forth as SEQ ID NO: 320. [Figure 19-20] Figure 19T shows analytical data for antibody-drug conjugates. Deconvoluted LC-MS spectra of hIgG1 ThioBridge®-Glu(-Gly3-EDA-PNU159682)-PEG(24u) conjugate (top spectrum) and mAb hIgG1 (bottom spectrum) are shown. The amino acid sequence EEEVX is set forth as SEQ ID NO: 319. The amino acid sequence EGGG is set forth as SEQ ID NO: 320. [Figure 19-21] Figure 19U shows analytical data for antibody-drug conjugates. Hydrophobic interaction chromatograms (A = 280 nm) for hIgG1 ThioBridge®-Glu(-Gly3-EDA-PNU159682)-PEG(24u) and mAb hIgG1 are shown. The amino acid sequence EEEVX is set forth as SEQ ID NO: 319. The amino acid sequence EGGG is set forth as SEQ ID NO: 320. [Figure 19-22] Figure 19V shows analytical data for antibody-drug conjugates. Size exclusion chromatograms (λ = 280 nm) for hlgG1 ThioBridge®-Glu(-Gly3-EDA-PNU159682)-PEG(24u) and a PBS blank are shown. The amino acid sequence EEEVX is set forth as SEQ ID NO: 319. The amino acid sequence EGGG is set forth as SEQ ID NO: 320. [Figure 20-1] Figure 20A shows HIC chromatograms of the antibody-drug conjugates tested. Figure 20B shows an HIC chromatogram of ThioBridge® non-cleavable PNU159682 ADC incubated in human serum for 96 hours. [Figure 20-2]Figure 20B shows HIC chromatograms of the antibody-drug conjugates tested. Shown is an HIC chromatogram of different lots of ThioBridge® "Glu-Val-Cit-PAB" PNU159682 ADC incubated in human serum for 96 hours. [Figure 20-3] Figure 20C shows HIC chromatograms of the antibody-drug conjugates tested. HIC chromatogram of ThioBridge® non-cleavable PNU159682 ADC incubated in mouse serum for 96 hours is shown. [Figure 20-4] Figure 20D shows HIC chromatograms of the antibody-drug conjugates tested. Shown is an HIC chromatogram of different lots of ThioBridge® "Glu-Val-Cit-PAB" PNU159682 ADC incubated in mouse serum for 96 hours. [Figure 20-5] Figure 20E shows HIC chromatograms of the antibody-drug conjugates tested, including blank mouse serum and hz143G03(N61Q) ThioBridge® "Glu-Val-Cit-PAB" cleavable PNU159682 incubated in mouse serum for 96 hours. [Figure 21] Development of the affinity capture method is shown. Deconvoluted LC-MS spectra of (1) (ADC starting material—h14A10 ThioBridge® “Glu-Val-Cit-PAB” cleavable PNU159682), (2) ADC captured from human serum, (3) ADC captured from mouse serum, and (4) ADC captured from PBS. [Figure 22-1] Figure 22A shows analysis of human and mouse serum. h14A10 ThioBridge® "Glu-Val-Cit-PAB" cleavable PNU159682 affinity captured from human serum after reduction with DTT and analyzed by LC-MS. [Figure 22-2]Figure 22B shows analysis of human and mouse serum. h14A10 ThioBridge® "Glu-Val-Cit-PAB" cleavable PNU159682 affinity captured from mouse serum after reduction with DTT and analyzed by LC-MS. [Figure 23-1] 1 shows reagent-related species investigated for the ThioBridge® non-cleavable PNU159682 reagent ADC. [Figure 23-2] Same as above. [Figure 24] 1 shows the reagent-related species investigated for the ThioBridge® “Glu-Val-Cit-PAB” cleavable PNU159682 reagent ADC. [Figure 25-1] Figure 25A shows the cytotoxicity of TDI-Y-004 and TDI-Y-005 ADCs on organoid models. A schematic diagram of the method for preparing organoid models is shown. [Figure 25-2] Figure 25B shows the cytotoxicity of TDI-Y-004 and TDI-Y-005 ADCs on an organoid model. Organoid growth in the presence of the indicated molecules is shown. [Figure 25-3] Figure 25C shows the cytotoxicity of TDI-Y-004 and TDI-Y-005 ADCs on organoid models. Figure 25D shows the modulation of organoid growth by L1CAM antibodies. [Figure 25-4] Figure 25D shows the cytotoxicity of TDI-Y-004 and TDI-Y-005 ADCs on organoid models. Organoid growth by L1CAM antibody-drug conjugates. [Figure 26]Figure 26A shows the in vivo antitumor efficacy of the TDI-Y-004 and TDI-Y-005 ADCs. Athymic mice were subcutaneously implanted with MDA-MB-231-LM2 breast cancer cells. Once tumors measuring 100 mm3 were established, the animals were administered a 4-week dose of ADCs generated using the L1CAM lead mAb (TDI-Y-004 and TDI-Y-005) with a cleavable (C) linker (0.3 mg / kg) or a non-cleavable (NC) linker (1 mg / kg), or a vehicle control and a human IgG1 isotype control (IgG) conjugated to PNU-159682 (PNU). Tumor growth was monitored weekly. Figure 26B shows the in vivo antitumor efficacy of the TDI-Y-004 and TDI-Y-005 ADCs. Athymic mice were subcutaneously implanted with MDA-MB-231-LM2 breast cancer cells. Once tumors measuring 100 mm3 were established, animals were administered a 4-week dose of ADCs generated using the L1CAM lead mAb (TDI-Y-004 and TDI-Y-005) with either a cleavable (C) linker (0.3 mg / kg) or a non-cleavable (NC) linker (1 mg / kg), or a vehicle control and a human IgG1 isotype control (IgG) conjugated to PNU-159682 (PNU). Tumor growth was monitored weekly. Figure 26C shows the in vivo antitumor efficacy of the TDI-Y-004 and TDI-Y-005 ADCs. Athymic mice were subcutaneously implanted with MDA-MB-231-LM2 breast cancer cells. Once tumors measuring 100 mm3 were established, animals were administered a 4-week dose of ADCs generated with the L1CAM lead mAb (TDI-Y-004 and TDI-Y-005) plus a cleavable (C) linker (0.3 mg / kg) or a non-cleavable (NC) linker (1 mg / kg), or a vehicle control and a human IgG1 isotype control (IgG) conjugated to PNU-159682 (PNU). Overall survival, monitored weekly, is shown. [Figure 27]Figure 27A shows the in vivo anti-pulmonary metastasis efficacy of the TDI-Y-004 and TDI-Y-005 ADCs. MDA-MB-231-LM2 breast cancer cells were introduced into athymic mice via tail vein injection to develop lung metastases. Animals were administered a 4-week dose of ADCs generated using the L1CAM lead mAb (TDI-Y-004 and TDI-Y-005) plus a cleavable (C) linker (0.3 mg / kg) or a non-cleavable (NC) linker (1 mg / kg), or a vehicle control and a human IgG1 isotype control (IgG) conjugated to PNU-159682 (PNU). Weekly monitored tumor growth is shown. Figure 27B shows the in vivo anti-pulmonary metastasis efficacy of the TDI-Y-004 and TDI-Y-005 ADCs. MDA-MB-231-LM2 breast cancer cells were introduced into athymic mice via tail vein injection to develop lung metastases. Animals were administered a 4-week dose of ADCs generated using the L1CAM lead mAb (TDI-Y-004 and TDI-Y-005) with either a cleavable (C) linker (0.3 mg / kg) or a non-cleavable (NC) linker (1 mg / kg), or a vehicle control and a human IgG1 isotype control (IgG) conjugated to PNU-159682 (PNU). Tumor growth was monitored weekly. Figure 27C shows the in vivo anti-pulmonary metastasis efficacy of the TDI-Y-004 and TDI-Y-005 ADCs. MDA-MB-231-LM2 breast cancer cells were introduced into athymic mice via tail vein injection to develop lung metastases. Animals were administered a 4-week dose of ADCs generated with the L1CAM lead mAb (TDI-Y-004 and TDI-Y-005) plus a cleavable (C) linker (0.3 mg / kg) or a non-cleavable (NC) linker (1 mg / kg), or a vehicle control and a human IgG1 isotype control (IgG) conjugated to PNU-159682 (PNU). Overall survival, monitored weekly, is shown. [Figure 28-1]Figure 28A shows the in vivo antitumor efficacy of the TDI-Y-005 ADC. Athymic mice were subcutaneously implanted with CRC107 cancer cells. Once tumors were established, animals were administered a 4-week dose of the ADC generated using the L1CAM lead TDI-Y-005 plus a cleavable (C) linker (0.3 mg / kg) or a non-cleavable (NC) linker (1 mg / kg), or a vehicle control and a human IgG1 isotype control (IgG) conjugated to PNU-159682 (PNU). In certain cohorts, mice were also administered irinotecan. Weekly monitored tumor volumes are shown. [Figure 28-2] Figure 28B shows the in vivo antitumor efficacy of the TDI-Y-005 ADC. Athymic mice were subcutaneously implanted with CRC107 cancer cells. Once tumors were established, animals were administered a 4-week dose of the ADC generated using the L1CAM lead TDI-Y-005 plus a cleavable (C) linker (0.3 mg / kg) or a non-cleavable (NC) linker (1 mg / kg), or a vehicle control and a human IgG1 isotype control (IgG) conjugated to PNU-159682 (PNU). In certain cohorts, mice were also administered irinotecan. Tumor volumes at 4 and 7 weeks of treatment are shown. [Figure 28-3] Figure 28C shows the in vivo antitumor efficacy of the TDI-Y-005 ADC. Athymic mice were subcutaneously implanted with CRC107 cancer cells. Once tumors were established, animals were administered a 4-week dose of the ADC generated using the L1CAM lead TDI-Y-005 plus a cleavable (C) linker (0.3 mg / kg) or a non-cleavable (NC) linker (1 mg / kg), or a vehicle control and a human IgG1 isotype control (IgG) conjugated to PNU-159682 (PNU). In certain cohorts, mice were also administered irinotecan. Tumor volumes at 4 and 7 weeks of treatment are shown. [Figure 29-1] Figure 29A shows the manufacturability study of TDI-Y-004. HPLC-SEC chromatograms are shown. [Figure 29-2]Figure 29B shows a manufacturability study of TDI-Y-004. Non-reduced CE-SDS chromatogram is shown. [Figure 29-3] Figure 29C shows a manufacturability study of TDI-Y-004. Reduced CE-SDS chromatogram is shown. [Figure 30-1] Figure 30 shows the manufacturability study of ATDI-Y-005. HPLC-SEC chromatograms are shown. [Figure 30-2] Figure 3 shows a manufacturability study of BTDI-Y-005. Non-reduced CE-SDS chromatogram is shown. [Figure 30-3] Figure 30 shows a manufacturability study of CTDI-Y-005. Reduced CE-SDS chromatogram is shown. [Figure 31-1] Figure 31A shows the structures of the cleavable and non-cleavable linkers utilized in generating the L1CAM ADC. The structure of the cleavable linker (ThioBridge®-Glu-(Glu-Val-Cit-PAB-DMAE-PNU-159682)-PEG(24u)) is shown. [Figure 31-2] Figure 31B shows the structures of the cleavable and non-cleavable linkers utilized in generating the L1CAM ADC. The structure of the non-cleavable linker (ThioBridge®-Glu-(Gly3-EDA-PNU-159682)-PEG(24u)) is shown. The ADC had an average drug-to-antibody ratio (DAR) of 4. [Figure 32-1] Figure 32A shows the binding of humanized 76H12 Fab variants. Flow cytometry is shown for binding to 293T cells engineered to overexpress L1CAM. [Figure 32-2] Figure 32B shows binding of humanized 76H12 Fab variants. Kinetic data of tested humanized variants binding to L1CAM-Fc fusion protein is shown. [Figure 33-1]Figure 33A shows the in vitro and in vivo efficacy of anti-L1CAM 13F04 ADC against human metastatic lung adenocarcinoma (LUAD) cells. Cell viability was assessed after 96 hours using CellTiterGlo reagent and normalized to DMSO control. Data are the average of triplicate samples from three independent experiments. Bars represent standard deviation. [Figure 33-2] Figure 33B shows the in vitro and in vivo efficacy of anti-L1CAM 13F04 ADC against human metastatic lung adenocarcinoma (LUAD) cells. Tumor growth monitored using BLI measurements is shown. Bars represent standard deviation. n=10 mice for 13F04 and 9 mice for the IgG ADC group. **P<0.01 DETAILED DESCRIPTION OF THE INVENTION

[0048] Metastatic cancer is the second leading cause of death in the United States (approximately 600,000 deaths per year). There is an unmet need for drugs that can target and eliminate therapy-resistant disease in patients with advanced solid tumors. The subject matter disclosed herein is based in part on the generation of novel anti-L1CAM antibodies that, when conjugated to a therapeutic agent, enable the elimination of quiescent metastatic stem cells. These antibodies or immunoconjugates of such antibodies can be complementary to chemotherapy and therapies that target rapidly proliferating cells. This new concept in cancer treatment can address the plasticity of advanced cancers that leads to metastatic recurrence after therapy. Non-limiting embodiments of the present disclosure are illustrated herein and in the examples.

[0049] For clarity of disclosure, and not by way of limitation, this detailed description is divided into the following subsections. 1. Definition, 2. L1CAM, 3. Anti-L1CAM antibody, 4. Immunoconjugates, 5. Nucleic acids encoding antibodies or antigen-binding fragments, 6. Pharmaceutical compositions and methods of treatment, 7. Diagnostic and prognostic methods, 8. Kits, and 9. Exemplary embodiment.

[0050] 1.Definition In the following description, certain rules regarding the use of terminology are followed: In general, the terms used herein are intended to be interpreted consistently with the meaning of those terms as known to those skilled in the art.

[0051] As these terms are known in the art, "antibody" and "antibody(s)" refer to antigen-binding proteins of the immune system. The term "antibody" referred to herein includes intact, full-length antibodies having an antigen-binding region, as well as "antigen-binding fragments" or any fragments thereof in which the "antigen-binding region" is retained, or a single chain thereof, e.g., single-chain variable fragments (scFv). A naturally occurring "antibody" is a glycoprotein comprising at least two heavy (H) chains and two light (L) chains interconnected by disulfide bonds. Each heavy chain comprises a heavy chain variable region (herein referred to as V H Each light chain consists of a light chain variable region (abbreviated herein as V) and a heavy chain constant region (CH). The heavy chain constant region is composed of three domains: CH1, CH2, and CH3. L ) and light chain constant C L The light chain constant region consists of one domain, C L It consists of V H Area and V L The regions can be further subdivided into regions of hypervariability, called complementarity-determining regions (CDRs), interspersed with more conserved regions, called framework regions (FRs). H and V Lis composed of three CDRs and four FRs, arranged from the amino terminus to the carboxy terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The variable regions of the heavy and light chains contain binding domains that interact with antigens. The constant region of the antibody can mediate the binding of the immunoglobulin to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (C1q) of the classical complement system.

[0052] As used herein, the term "antigen-binding fragment" or "antigen-binding region" of an antibody refers to a region or fragment of an antibody that binds to an antigen and confers antigen specificity to the antibody, and fragments of antigen-binding proteins, e.g., antibodies, include one or more fragments of an antibody that retain the ability to specifically bind to an antigen (e.g., an L1CAM polypeptide). It has been shown that the antigen-binding function of an antibody can be performed by fragments of a full-length antibody. Examples of antigen-binding fragments encompassed by the term "antibody fragment" of an antibody include V L , V H , C L and a Fab fragment, which is a monovalent fragment consisting of a CH1 domain; a F(ab)2 fragment, which is a bivalent fragment containing two Fab fragments linked by a disulfide bridge at the hinge region; a V H and an Fd fragment consisting of the CH1 domain, a V fragment of a single arm of the antibody L Domains and V H Fv fragment consisting of domains, V H These include dAb fragments consisting of domains (Ward et al., Nature 1989;341:544-546), as well as isolated complementarity determining regions (CDRs).

[0053] Furthermore, the two domains V of the Fv fragment L and V H are encoded by separate genes, but these are collectively referred to as V L Area and V HThe regions can be joined using recombinant methods by synthetic linkers that allow them to be produced as a single protein chain that pairs to form a monovalent molecule. These are known as single-chain Fvs (scFvs); see, e.g., Bird et al., Science (1988); 242:423-426, and Huston et al., Proc Natl Acad Sci (1998); 85:5879-5883. These antibody fragments are obtained using conventional techniques known to those skilled in the art, and the fragments are screened for utility in the same manner as intact antibodies.

[0054] The term "human antibody," as used herein, is intended to include antibodies having variable regions in which both the framework and CDR regions are derived from human germline immunoglobulin sequences. Furthermore, if the antibody contains a constant region, the constant region also is derived from human germline immunoglobulin sequences. The human antibodies of the presently disclosed subject matter may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo).

[0055] As used herein, the term "monoclonal antibody" refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical and / or bind to the same epitope, except for possible variant antibodies, which may contain, for example, naturally occurring mutations or arise during production of the monoclonal antibody preparation, and are generally present in minor amounts. In contrast to polyclonal antibody preparations, which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody of a monoclonal antibody preparation is directed against a single determinant on an antigen. Thus, the modifier "monoclonal" indicates the character of the antibody as being obtained from a substantially homogeneous antibody population and should not be construed as requiring production of the antibody by any particular method. For example, monoclonal antibodies used in accordance with the subject matter disclosed herein may be produced by a variety of techniques, including, but not limited to, hybridoma methods, recombinant DNA methods, phage display methods, and methods utilizing transgenic animals containing all or part of the human immunoglobulin loci, as well as other exemplary methods for producing monoclonal antibodies described herein.

[0056] As used herein, the term "recombinant human antibody" includes all human antibodies prepared, expressed, generated, or isolated by recombinant means, e.g., (a) antibodies isolated from animals (e.g., mice) that are transgenic or transchromosomal for human immunoglobulin genes or hybridomas prepared therefrom (described further below); (b) antibodies isolated from host cells that have been transformed to express human antibodies, e.g., from transfectomas; (c) antibodies isolated from recombinant combinatorial human antibody libraries; and (d) antibodies prepared, expressed, generated, or isolated by any other means involving splicing of human immunoglobulin gene sequences to other DNA sequences. Such recombinant human antibodies have variable regions in which the framework and CDR regions are derived from human germline immunoglobulin sequences. However, in certain embodiments, such recombinant human antibodies may be subjected to in vitro mutagenesis (or, when animals transgenic for human Ig sequences are used, in vivo somatic mutagenesis), thus allowing for the development of recombinant antibody Vs. H Area and V L The amino acid sequence of the region is human germline V H Array and V L These are sequences that, while derived from and related to a sequence, may not naturally occur in the human antibody germline repertoire in vivo.

[0057] The term "humanized antibody" is intended to refer to antibodies in which CDR sequences derived from the germline of another mammalian species, such as a mouse, have been grafted onto human framework sequences. Additional framework region modifications may be made within the human framework sequences.

[0058] The term "chimeric antibody" is intended to refer to an antibody in which the variable region sequences are derived from one species and the constant region sequences are derived from another species, e.g., the variable region sequences are derived from a murine antibody and the constant region sequences are derived from a human antibody.

[0059] As used herein, an antibody that "specifically binds to L1CAM" is an antibody that specifically binds to L1CAM in an amount of about 1 x 10-8 M or less, about 5 x 10 -9 M or less, approximately 1×10 -9 M or less, about 5 x 10 -10 M or less, approximately 1×10 -10 M or less, about 5 x 10 -11 M or less, or approximately 1 x 10 -11 The dissociation constant (K D ) is intended to refer to an antibody that binds to L1CAM (e.g., human L1CAM).

[0060] An "antibody that competes for binding" or "antibody that cross-competes for binding" with a reference antibody for binding to an antigen, e.g., L1CAM, refers to an antibody that blocks the binding of the reference antibody to an antigen (e.g., L1CAM) by 50% or more in a competition assay, and conversely, the reference antibody blocks the binding of the antibody to the antigen (e.g., L1CAM) by 50% or more in a competition assay. Exemplary competition assays are described in "Antibodies," Harlow and Lane (Cold Spring Harbor Press, Cold Spring Harbor, NY).

[0061] As used herein, "isotype" refers to the antibody class (e.g., IgM or IgG1) that is encoded by heavy chain constant region genes.

[0062] The phrases "antibody that recognizes an antigen" and "antibody specific for an antigen" may be used interchangeably herein with the term "antibody that specifically binds to an antigen (eg, an L1CAM polypeptide)."

[0063] As used herein, the term "single-chain variable fragment" or "scFv" refers to a V H ::V L Heavy chains (V) of immunoglobulins (e.g., mouse or human) covalently linked to form heterodimers H ) and light chain (V L ) is a fusion protein of the variable region of the heavy chain (V H ) and light chain (V L) are either directly connected or connected by a linker encoding a peptide (e.g., 10, 15, 20, 25 amino acids), and V H N-terminus of V L or V H The C-terminus of V L The linker is typically rich in glycine for flexibility and serine or threonine for solubility. The linker can connect the heavy and light chain variable regions of the extracellular antigen-binding domain.

[0064] For example, non-limiting examples of linkers for use in generating scFvs are disclosed in Shen et al., Anal Chem (2008); 80(6): 1910-1917 and WO2014 / 087010, the contents of which are incorporated herein by reference in their entireties. In certain embodiments, the linker is a G4S linker. In certain embodiments, the linker comprises or consists of the amino acid sequence set forth in SEQ ID NO: 138, provided below: GGGGSGGGGSGGGSGGGGS [SEQ ID NO: 138]

[0065] In certain embodiments, the linker comprises or consists of the amino acid sequence set forth in SEQ ID NO: 139, provided below: GGGGSGGGGSGGGGS [SEQ ID NO: 139]

[0066] In certain embodiments, the linker comprises or consists of the amino acid sequence set forth in SEQ ID NO: 140, provided below: GGGGSGGGGSGGGGSGGGSGGGGS [SEQ ID NO: 140]

[0067] In certain embodiments, the linker comprises or consists of the amino acid sequence set forth in SEQ ID NO: 141, provided below: GGGGSGGGGSGGGGSGGGGSGGGSGGGGS [SEQ ID NO: 141]

[0068] In certain embodiments, the linker comprises or consists of the amino acid sequence set forth in SEQ ID NO: 142, provided below: GGGGS [SEQ ID NO: 142]

[0069] In certain embodiments, the linker comprises or consists of the amino acid sequence set forth in SEQ ID NO: 143, provided below: GGGGSGGGGS [SEQ ID NO: 143]

[0070] Despite the removal of the constant region and the introduction of the linker, the scFv protein retains the specificity of the original immunoglobulin. Single-chain Fv polypeptide antibodies are synthesized using the V, ... H and V LThe polypeptide can be expressed from a nucleic acid containing a sequence encoding the polypeptide. See also U.S. Patent Nos. 5,091,513, 5,132,405, and 4,956,778, and U.S. Patent Publication Nos. 2005 / 0196754 and 2005 / 0196754. Antagonistic scFvs with inhibitory activity have been described (e.g., Zhao et al., Hyrbidoma (Larchmt) 2008;27(6):455-51; Peter et al., J Cachexia Sarcopenia Muscle 2012 August 12; Shieh et al., J Imunol 2009;183(4):2277-85; Giomarelli et al., Thromb Haemost 2007;97(6):955-63; Fife et al., J Clin Invst 2006;116(8):2252-61; Brocks et al., Immunotechnology 1997;3(3):173-84; Moosmayer et al., Ther Immunol 1995;2 (10:31-40). Agonistic scFvs with stimulatory activity have been described (see, e.g., Peter et al., J Bio. Chem 2003;25278(38):36740-7; Xie et al., Nat Biotech 1997;15(8):768-71; Ledbetter et al., Crit Rev Immunol 1997;17(5-6):427-55; Ho et al., BioChim Biophys Acta 2003;1638(3):257-66).

[0071] As used herein, "F(ab)" refers to the fragment of an antibody structure that binds to an antigen but is monovalent and does not have the Fc portion; for example, digestion of an antibody with the enzyme papain yields two F(ab) fragments and an Fc fragment (heavy (H) chain constant region, the Fc region that does not bind to antigen).

[0072] As used herein, "F(ab')2" refers to an antibody fragment produced by pepsin digestion of a whole IgG antibody, which fragment has two antigen-binding (ab') (bivalent) regions, each (ab') region containing two separate amino acid chains, a portion of an H chain and a light (L) chain, linked by an S-type disulfide bond to bind the antigen, with the remaining H chain portions linked together. The "F(ab')2" fragment can be separated into two individual Fab' fragments.

[0073] As used herein, the term "vector" refers to any genetic element, such as a plasmid, phage, transposon, cosmid, chromosome, virus, virion, etc., that is capable of replicating and transferring genetic sequences into a cell when associated with the appropriate control elements. Thus, the term includes cloning and expression vehicles, as well as viral and plasmid vectors.

[0074] "CDR" is defined as the complementarity-determining region amino acid sequence of an antibody, which is the hypervariable region of immunoglobulin heavy and light chains. See, for example, Kabat et al., Sequences of Proteins of Immunological Interest, 4th USD Department of Health and Human Services, National Institutes of Health (1987), or the IMGT numbering system (Lefranc, The Immunologist (1999); 7:132-136; Lefranc et al., Dev. Comp. Immunol. (2003); 27:55-77). As used herein, the term "hypervariable region" or "HVR" refers to each of the regions of an antibody variable domain whose sequence is hypervariable ("complementarity-determining region" or "CDR") and / or forms a structurally defined loop ("hypervariable loop") and / or contains antigen-contact residues ("antigen contact"). Generally, an antibody contains three heavy chain and three light chain CDRs or CDR regions in the variable region. CDR provides the majority of contact residues for antibody binding to antigen or epitope region.In certain embodiments, CDR is identified according to the IMGT system.In certain embodiments, CDR is identified using the IMGT numbering system, which can be accessed at http: / / www.imgt.org / IMGT_vquest / input.

[0075] The term "isolated" refers to the degree of separation from the original source or surroundings.

[0076] An "isolated antibody" is one that has been separated from a component of its natural environment. In certain embodiments, the antibody is purified to greater than 95% or 99% purity, as determined, for example, by electrophoresis (e.g., SDS-PAGE, isoelectric focusing (IEF), capillary electrophoresis) or chromatography (e.g., ion exchange or reverse-phase HPLC). For a review of methods for assessing antibody purity, see, for example, Flatman et al., J. Chromatogr (2007); B 848:79-87.

[0077] An "isolated nucleic acid" refers to a nucleic acid molecule that has been separated from a component of its natural environment. Isolated nucleic acid includes a nucleic acid molecule contained within a cell that ordinarily contains the nucleic acid molecule, but where the nucleic acid molecule is present extrachromosomally or at a chromosomal location that is different from its natural chromosomal location.

[0078] An "isolated nucleic acid encoding an antibody" (including reference to a particular antibody, e.g., an anti-L1CAM antibody) refers to one or more nucleic acid molecules encoding the heavy and light chains (or fragments thereof) of an antibody, including such nucleic acid molecule(s) in a single vector, separate vectors, and such nucleic acid molecule(s) present in one or more locations in a host cell.

[0079] The term "vector," as used herein, refers to a nucleic acid molecule capable of propagating another nucleic acid to which it is linked. The term includes vectors as self-replicating nucleic acid structures as well as vectors that have integrated into the genome of a host cell into which they have been introduced. Certain vectors are capable of directing the expression of nucleic acids to which they are operatively linked. Such vectors are referred to herein as "expression vectors."

[0080] An "immunoconjugate" is an antibody conjugated to one or more heterologous molecule(s), including, but not limited to, a cytotoxic agent.

[0081] An "effective amount" (or "therapeutically effective amount") is an amount sufficient to produce beneficial or desired clinical results upon treatment. An effective amount can be administered to a subject in one or more doses. From a therapeutic perspective, an effective amount is an amount sufficient to palliate, ameliorate, stabilize, reverse, or slow the progression of a disease, or otherwise reduce the pathological consequences of a disease. An effective amount is generally determined by a physician on a case-by-case basis and is within the skill of one of ordinary skill in the art. Several factors are typically considered when determining the appropriate dosage to achieve an effective amount. These factors include the age, sex, and weight of the subject, the condition being treated, the severity of the condition, and the form and effective concentration of the cells administered.

[0082] As used herein, an "individual" or "subject" refers to a vertebrate, e.g., a human or a non-human animal, e.g., a mammal. Mammals include, but are not limited to, humans, primates, farm animals, sport animals, rodents, and pets. Non-limiting examples of non-human animal subjects include rodents such as mice, rats, and hamsters, guinea pigs, rabbits, dogs, cats, sheep, pigs, goats, cows, horses, and non-human primates such as apes and monkeys.

[0083] As used herein, "treatment" (and grammatical variants thereof, e.g., "treat" or "treating") refers to clinical intervention in an attempt to alter the natural course of the individual being treated and can be performed either for prophylaxis or during the course of clinical pathology. Desirable effects of treatment include, but are not limited to, preventing the occurrence or recurrence of disease, alleviation of symptoms, mitigation of any direct or indirect pathological consequences of the disease, preventing metastasis, reducing the rate of disease progression, amelioration or amelioration of the disease state, and remission or improved prognosis. In certain embodiments, the antibodies of the presently disclosed subject matter are used to delay the onset of disease or to slow the progression of a disease, e.g., a tumor, e.g., an L1CAM-associated tumor.

[0084] The terms "comprises" and "comprising" are intended to have the broad meaning ascribed to them in U.S. patent law and may mean "includes," "including," etc.

[0085] As used herein, the term "about" or "approximately" means within an acceptable error range for a particular value as determined by one of ordinary skill in the art, which depends in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, "about" can mean within 3 or more than 3 standard deviations, according to practice in the art. Alternatively, "about" can mean a range of up to 20%, preferably up to 10%, more preferably up to 5%, and even more preferably up to 1% of a given value. Alternatively, particularly with respect to biological systems or processes, the term can mean within one order of magnitude of a value, preferably within 5-fold, and more preferably within 2-fold.

[0086] As described herein, any concentration range, percentage range, ratio range, or integer range should be understood to include any integer value within the recited range, and fractions thereof (such as integer tenths and hundredths), where appropriate, unless otherwise indicated.

[0087] Other aspects of the presently disclosed subject matter are described in the disclosure that follows and are within the scope of the presently disclosed subject matter.

[0088] 2. L1CAM L1CAM, encoded by the L1CAM gene, is a transmembrane protein member of the L1 protein family. This approximately 200–220 kDa protein is a neural cell adhesion molecule that is closely related to cell migration, adhesion, neurite outgrowth, myelination, and neuronal differentiation (Samatov et al., Prog Histochem Cytochem. 2016 Aug;51(2):25–32).

[0089] L1CAM is composed of six IgG domains, three fibronectin type III domains, and a short cytoplasmic domain. The extracellular domain forms homophilic and heterophilic interactions with integrins and several extracellular matrix proteins. Through its cytoplasmic tail, L1CAM binds to ezrin, ankyrin, and other signaling adaptor proteins. L1CAM is primarily expressed by developing neurons, where it regulates axon outgrowth and synapse formation, but is also found in certain hematologic and endothelial cell types. Notably, cancer cells exclusively express non-neuronal splice forms of L1CAM, and these isoforms have recently been discovered to be naturally expressed in pericytes, contractile mesenchymal cells that wrap around capillaries to regulate blood flow. L1CAM is involved in the metastatic growth of multiple solid tumors, including the three most prominent causes of cancer death (e.g., lung, breast, and colorectal cancer), as well as in multiple organ sites (e.g., bone, lung, liver, and brain). Furthermore, L1CAM is involved in the proliferation of invasive cancer cells immediately after they have newly seeded target organs, as well as indolent cancer cells that emerge from dormancy. L1CAM is required for the initiation of micrometastases, the maintenance and spread of established metastases, and the resumption of metastatic growth by dormant micrometastases.

[0090] In certain embodiments, an anti-L1CAM antibody or antigen-binding fragment thereof disclosed herein binds to human L1CAM. In certain embodiments, human L1CAM comprises or consists of the amino acid sequence having UniProt Reference Number: P32004 (SEQ ID NO: 1) or a fragment thereof. SEQ ID NO: 1 is provided below. In certain embodiments, human L1CAM comprises an extracellular domain, a transmembrane domain, and a cytoplasmic domain. In certain embodiments, the extracellular domain comprises or consists of amino acids 20-1120 of SEQ ID NO: 1. In certain embodiments, the transmembrane domain comprises or consists of amino acids 1121-1143 of SEQ ID NO: 1. In certain embodiments, the cytoplasmic domain comprises or consists of amino acids 1144-1257 of SEQ ID NO: 1. MVVALRYVWPLLLCSPCLLIQIPEEYEGHHVMEPPVITEQSPRRLVVFPTDDISLKCEAS GKPEVQFRWTRDGVHFKPKEELGVTVYQSPHSGSFTITGNNSNFAQRFQGIYRCFASNKL GTAMSHEIRLMAEGAPKWPKETVKPVEVEEGESVVLPCNPPPSAEPLRIYWMNSKILHIK QDERVTMGQNGNLYFANVLTSDNHSDYICHAHFPGTRTIIQKEPIDLRVKATNSMIDRKP RLLFPTNSSSHLVALQGQPLVLECIAEGFPTPTIKWLRPSGPMPADRVTYQNHNKTLQLL KVGEEDDGEYRCLAENSLGSARHAYYVTVEAAPYWLHKPQSHLYGPGETARLDCQVQGRP QPEVTWRINGIPVEELAKDQKYRIQRGALILSNVQPSDTTMVTQCEARNRHGLLLANAYIY VVQLPAKILTADNQTYMAVQGSTAYLLCKAFGAPVPSVQWLDEDGTTVLQDERFFPYANG TLGIRDLQANDTGRYFCLAANDQNNVTIMANLKVKDATQITQGPRSTIEKKGSRVTFTCQ ASFDPSLQPSITWRGDGRDLQELGDSDKYFIEDGRLVIHSLDYSDQGNYSCVASTELDVV ESRAQLLVVGSPGPVPRLVLSDLHLLTQSQVRVSWSPAEDHNAPIEKYDIEFEDKEMAPE KWYSLGKVPGNQTSTTLKLSPYVHYTFRVTAINKYGPGEPSPVSETVVTPEAAPEKNPVD VKGEGNETTNMVITWKPLRWMDWNAPQVQYRVQWRPQGTRGPWQEQIVSDPFLVVSNTST FVPYEIKVQAVNSQGKGPEPQVTIGYSGEDYPQAIPELEGIEILNSSAVLVKWRPVDLAQ VKGHLRGYNVTYWREGSQRKHSKRHIHKDHVVVPANTTSVILSGLRPYSSYHLEVQAFNG RGSGPASEFTFSTPEGVPGHPEALHLECQSNTSLLLRWQPPLSHNGVLTGYVLSYHPLDE GGKGQLSFNLRDPELRTHNLTDLSPHLRYRFQLQATTKEGPGEAIVREGGTMALSGISDF GNISATAGENYSVVSWVPKEGQCNFRFHILFKALGEEKGGASLSPQYVSYNQSSYTQWDL QPDTDYEIHLFKERMFRHQMAVKTNGTGRVRLPPAGFATEGWFIGFVSAIILLLLVLLIL CFIKRSKGGKYSVKDKEDTQVDSEARPMKDETFGEYRSLESDNEEKAFGSSQPSLNGDIK PLGSDDSLADYGGSVDVQFNEDGSFIGQYSGKKEKEAAGGNDSSGATSPINPAVALE [SEQ ID NO: 1]

[0091] In certain embodiments, L1CAM comprises or consists of an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 1 or a fragment thereof.

[0092] In certain embodiments, the anti-L1CAM antibodies or antigen-binding fragments thereof disclosed herein bind to a portion of human L1CAM. In certain embodiments, the anti-L1CAM antibodies or antigen-binding fragments thereof disclosed herein bind to the extracellular domain of L1CAM. In certain embodiments, the anti-L1CAM antibodies or antigen-binding fragments thereof disclosed herein bind to amino acids 20 to 1120 of SEQ ID NO: 1.

[0093] 3. Anti-L1CAM antibody The antibodies of the presently disclosed subject matter are characterized by a particular functional feature or property of the antibody, for example, the antibody specifically binds to L1CAM (e.g., binds to human L1CAM).

[0094] In certain embodiments, the antibodies or antigen-binding fragments disclosed herein bind to L1CAM (e.g., human L1CAM) with a binding affinity of, for example, 1×10 -8 M or less, for example, about 1 × 10 -8 M or less, about 5 x 10 -9 M or less, approximately 1×10 -9 M or less, about 5 x 10 -10 M or less, approximately 1×10 -10 M or less, or approximately 1 x 10 -11 The dissociation constant (K D In certain embodiments, the anti-L1CAM antibody or antigen-binding fragment thereof disclosed herein binds at about 5×10 -9 K below M D In certain embodiments, the anti-L1CAM antibodies or antigen-binding fragments thereof disclosed herein bind to L1CAM (e.g., human L1CAM) at a concentration of about 1 x 10 -9 K below MD In certain embodiments, the anti-L1CAM antibodies or antigen-binding fragments thereof disclosed herein bind to L1CAM (e.g., human L1CAM) at a concentration of about 1 x 10 -10 K below M D In certain embodiments, the anti-L1CAM antibodies or antigen-binding fragments thereof disclosed herein bind to L1CAM (e.g., human L1CAM) at a concentration of about 1 x 10 -9 M ~ approx. 1×10 -10 K of M D In certain embodiments, the anti-L1CAM antibodies or antigen-binding fragments thereof disclosed herein bind to L1CAM (e.g., human L1CAM) at a concentration of about 1 x 10 -10 M ~ approx. 1×10 -11 K of M D In certain embodiments, the anti-L1CAM antibodies or antigen-binding fragments thereof disclosed herein bind to L1CAM (e.g., human L1CAM) at a concentration of about 1 x 10 -10 K of M D In certain embodiments, the anti-L1CAM antibodies or antigen-binding fragments thereof disclosed herein bind to L1CAM (e.g., human L1CAM) at a concentration of about 2×10 -11 K of M D It binds to L1CAM (e.g., human L1CAM) at

[0095] In certain embodiments, the antibodies or antigen-binding fragments disclosed herein have a half-maximal effective concentration (EC) of about 1 nM to about 50 nM, about 5 nM to about 50 nM, about 10 nM to about 50 nM, about 20 nM to about 50 nM, about 30 nM to about 50 nM, about 40 nM to about 50 nM, or greater than about 50 nM. 50 In certain embodiments, the antibodies or antigen-binding fragments disclosed herein bind to cells expressing L1CAM (e.g., metastatic cells expressing L1CAM) with an EC value of about 1 nM to about 5 nM. 50 In certain embodiments, the antibodies or antigen-binding fragments disclosed herein bind to cells expressing L1CAM (e.g., metastatic cells expressing L1CAM) with an EC value of about 1 nM. 50In certain embodiments, the antibodies or antigen-binding fragments disclosed herein bind to cells expressing L1CAM (e.g., metastatic cells expressing L1CAM) with an EC value of about 4.8 nM. 50 It binds to cells expressing L1CAM (e.g., metastatic cells expressing L1CAM) at low levels.

[0096] The heavy and light chains of the antibodies or antigen-binding fragments disclosed herein can be full-length (e.g., an antibody can comprise at least one (e.g., one or two) complete heavy chains and at least one (e.g., one or two) complete light chains), or can comprise an antigen-binding fragment (Fab, F(ab'), Fv, or single-chain Fv fragment ("scFv")). In certain embodiments, the antibody heavy chain constant region is selected from, e.g., IgG1, IgG2, IgG3, IgG4, IgM, IgA1, IgA2, IgD, and IgE. In certain embodiments, the antibody heavy chain constant region is selected from, e.g., IgG1, IgG2, IgG3, and IgG4. In certain embodiments, the immunoglobulin isotype is IgG1 (e.g., human IgG1). The choice of antibody isotype can depend on the immune effector function the antibody is designed to elicit. In certain embodiments, the antibody light chain constant region is selected from, e.g., kappa or lambda. In certain embodiments, the antibody light chain constant region is kappa.

[0097] In constructing recombinant immunoglobulins, the appropriate amino acid sequences for the constant regions of various immunoglobulin isotypes and methods for producing a wide range of antibodies are known to those skilled in the art.

[0098] 3.1. Single-chain variable fragments (scFv) In certain embodiments, the presently disclosed subject matter includes antibodies or antigen-binding fragments thereof in which an scFv sequence is fused to one or more constant domains to form an antibody with the Fc region of a human immunoglobulin, resulting in a bivalent protein and increasing the overall avidity and stability of the antibody. In addition, the Fc portion allows other molecules, including but not limited to, fluorescent dyes, cytotoxins, radioisotopes, etc., to be directly conjugated to the antibody, for example, for use in antigen quantification studies, for affinity measurements, for targeted delivery of therapeutic agents, for testing Fc-mediated cytotoxicity using immune effector cells, and many other applications. In certain embodiments, the Fc portion is conjugated to a cytotoxin.

[0099] The results presented herein highlight the specificity, sensitivity and utility of the antibodies or antigen-binding fragments disclosed herein that target an L1CAM polypeptide (eg, a human L1CAM polypeptide).

[0100] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 1. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO:9. L SEQ ID NOs: 8 and 9 are provided in Table 1. In certain embodiments, the scFv is designated "scFv-Y-005."

[0101] In certain embodiments, the anti-L1CAM scFv comprises a V scFv comprising the amino acid sequence set forth in SEQ ID NO:8. H and V comprising the amino acid sequence set forth in SEQ ID NO:9 L Includes.

[0102] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:2 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:3 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:4 or a conservative modification thereof. H SEQ ID NOs: 2 to 4 are provided in Table 1.

[0103] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 5 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 6 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 7 or a conservative modification thereof. L SEQ ID NOs: 4 to 6 are provided in Table 1.

[0104] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 2 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 3 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 4 or a conservative modification thereof. H and a V comprising a CDR1 having the amino acid sequence set forth in SEQ ID NO: 5 or a conservative modification thereof, a CDR2 having the amino acid sequence set forth in SEQ ID NO: 6 or a conservative modification thereof, and a CDR3 having the amino acid sequence set forth in SEQ ID NO: 7 or a conservative modification thereof. L Includes:

[0105] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:2, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:3, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:4. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO:5, CDR2 having the amino acid sequence set forth in SEQ ID NO:6, and CDR3 having the amino acid sequence set forth in SEQ ID NO:7. L Includes:

[0106] In certain embodiments, the anti-L1CAM scFv comprises a V scFv comprising the amino acid sequence set forth in SEQ ID NO:8. H and V comprising the amino acid sequence set forth in SEQ ID NO:9 L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0107] In certain embodiments, the variable region is a heavy chain variable region (V H ) are located at the N-terminus. In certain embodiments, the variable regions are arranged from the N-terminus to the C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H .

[0108] In certain embodiments, the anti-L1CAM antibody is an antibody having a heavy chain and a light chain selected from Table 1. In certain embodiments, the anti-L1CAM antibody comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 10. In certain embodiments, the anti-L1CAM antibody comprises a light chain comprising the amino acid sequence set forth in SEQ ID NO: 11. SEQ ID NOs: 10 and 11 are provided in Table 1. In certain embodiments, the anti-L1CAM antibody is designated "TDI-Y-005." [Table 1-1] [Table 1-2]

[0109] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 2. H Area and VL In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 19. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 18. H and V comprising the amino acid sequence set forth in SEQ ID NO: 19. L SEQ ID NOs: 18 and 19 are provided in Table 2. In certain embodiments, the scFv is designated "scFv-Y-004."

[0110] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H SEQ ID NOs: 12-14 are provided in Table 2.

[0111] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 2.

[0112] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. Hand a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0113] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0114] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 18. H and V comprising the amino acid sequence set forth in SEQ ID NO: 19. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0115] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H .

[0116] In certain embodiments, the anti-L1CAM antibody is an antibody having a heavy chain and a light chain selected from Table 2. In certain embodiments, the anti-L1CAM antibody comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 20. In certain embodiments, the anti-L1CAM antibody comprises a light chain comprising the amino acid sequence set forth in SEQ ID NO: 21. SEQ ID NOs: 20 and 21 are provided in Table 2. In certain embodiments, the anti-L1CAM antibody is designated "TDI-Y-004." [Table 2-1] [Table 2-2]

[0117] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 3. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 23. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 22. H and V comprising the amino acid sequence set forth in SEQ ID NO: 23. L SEQ ID NOs: 22 and 23 are provided in Table 3. In certain embodiments, the scFv is designated "k1-h1."

[0118] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H SEQ ID NOs: 12-14 are provided in Table 3.

[0119] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 3.

[0120] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0121] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0122] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 22. H and V comprising the amino acid sequence set forth in SEQ ID NO: 23. L In certain embodiments, V H and V Lare linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0123] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 3]

[0124] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 4. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 23. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO:24. H and V comprising the amino acid sequence set forth in SEQ ID NO: 23. L SEQ ID NOs: 24 and 23 are provided in Table 4. In certain embodiments, the scFv is designated "k1-h2."

[0125] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H SEQ ID NOs: 12-14 are provided in Table 4.

[0126] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 4.

[0127] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0128] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0129] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 24. H and V comprising the amino acid sequence set forth in SEQ ID NO: 23. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0130] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 4]

[0131] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 5. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 23. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 25. H and V comprising the amino acid sequence set forth in SEQ ID NO: 23. LSEQ ID NOs: 25 and 23 are provided in Table 5. In certain embodiments, the scFv is designated "k1-h3."

[0132] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H SEQ ID NOs: 12-14 are provided in Table 5.

[0133] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 5.

[0134] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0135] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14. Hand a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes.

[0136] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 25. H and V comprising the amino acid sequence set forth in SEQ ID NO: 23. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0137] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 5]

[0138] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 6. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 23. LIn certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO:27. H and V comprising the amino acid sequence set forth in SEQ ID NO: 23. L SEQ ID NOs: 27 and 23 are provided in Table 6. In certain embodiments, the scFv is designated "k1-h4."

[0139] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof. H SEQ ID NOs: 12, 13, and 26 are provided in Table 6.

[0140] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 6.

[0141] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0142] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes.

[0143] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO:27. H and V comprising the amino acid sequence set forth in SEQ ID NO: 23. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0144] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 6]

[0145] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 7. H Area and V LIn certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 23. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO:28. H and V comprising the amino acid sequence set forth in SEQ ID NO: 23. L SEQ ID NOs: 28 and 23 are provided in Table 7. In certain embodiments, the scFv is designated "k1-h5."

[0146] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H SEQ ID NOs: 12-14 are provided in Table 7.

[0147] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 7.

[0148] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. Hand a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0149] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0150] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 28. H and V comprising the amino acid sequence set forth in SEQ ID NO: 23. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0151] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 7]

[0152] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 8. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 23. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO:29. H and V comprising the amino acid sequence set forth in SEQ ID NO: 23. L SEQ ID NOs: 29 and 23 are provided in Table 8. In certain embodiments, the scFv is designated "k1-h6."

[0153] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof. H SEQ ID NOs: 12, 13, and 26 are provided in Table 8.

[0154] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 8.

[0155] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0156] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0157] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO:29. H and V comprising the amino acid sequence set forth in SEQ ID NO: 23. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0158] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 8-1] [Table 8-2]

[0159] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 9. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 30. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 22. H and V comprising the amino acid sequence set forth in SEQ ID NO: 30 L SEQ ID NOs: 22 and 23 are provided in Table 9. In certain embodiments, the scFv is designated "k2-h1."

[0160] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H SEQ ID NOs: 12-14 are provided in Table 9.

[0161] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 9.

[0162] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0163] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14. H and V comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0164] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 22. H and V comprising the amino acid sequence set forth in SEQ ID NO: 30 L In certain embodiments, V H and V Lare linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0165] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 9]

[0166] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 10. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 30. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO:24. H and V comprising the amino acid sequence set forth in SEQ ID NO: 30 L SEQ ID NOs: 24 and 23 are provided in Table 10. In certain embodiments, the scFv is designated "k2-h2."

[0167] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H SEQ ID NOs: 12-14 are provided in Table 10.

[0168] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 10.

[0169] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes.

[0170] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes.

[0171] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 24. H and V comprising the amino acid sequence set forth in SEQ ID NO: 30 L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0172] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 10]

[0173] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 11. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 30. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 25. H and V comprising the amino acid sequence set forth in SEQ ID NO: 30 LSEQ ID NOs: 25 and 30 are provided in Table 11. In certain embodiments, the scFv is designated "k2-h3."

[0174] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H SEQ ID NOs: 12-14 are provided in Table 11.

[0175] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 11.

[0176] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0177] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14. Hand a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0178] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 25. H and V comprising the amino acid sequence set forth in SEQ ID NO: 30 L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0179] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 11-1] [Table 11-2]

[0180] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 12. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. HIn certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 30. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO:27. H and V comprising the amino acid sequence set forth in SEQ ID NO: 30 L SEQ ID NOs: 27 and 30 are provided in Table 12. In certain embodiments, the scFv is designated "k2-h4."

[0181] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof. H SEQ ID NOs: 12, 13, and 26 are provided in Table 12.

[0182] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 12.

[0183] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0184] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0185] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO:27. H and V comprising the amino acid sequence set forth in SEQ ID NO: 30 L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0186] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 12]

[0187] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 13. H Area and V LIn certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 30. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO:28. H and V comprising the amino acid sequence set forth in SEQ ID NO: 30 L SEQ ID NOs: 28 and 30 are provided in Table 13. In certain embodiments, the scFv is designated "k2-h5."

[0188] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H SEQ ID NOs: 12-14 are provided in Table 13.

[0189] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 13.

[0190] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. Hand a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0191] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0192] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 28. H and V comprising the amino acid sequence set forth in SEQ ID NO: 30 L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0193] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 13]

[0194] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 14. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 30. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO:29. H and V comprising the amino acid sequence set forth in SEQ ID NO: 30 L SEQ ID NOs: 29 and 30 are provided in Table 14. In certain embodiments, the scFv is designated "k2-h6."

[0195] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof. H SEQ ID NOs: 12, 13, and 26 are provided in Table 14.

[0196] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 14.

[0197] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes.

[0198] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes.

[0199] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO:29. H and V comprising the amino acid sequence set forth in SEQ ID NO: 23. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0200] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 14]

[0201] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 15. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 31. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 22. H and V comprising the amino acid sequence set forth in SEQ ID NO: 31. L SEQ ID NOs: 22 and 31 are provided in Table 15. In certain embodiments, the scFv is designated "k3-h1."

[0202] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H SEQ ID NOs: 12-14 are provided in Table 15.

[0203] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. LSEQ ID NOs: 15-17 are provided in Table 15.

[0204] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0205] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0206] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 22. H and V comprising the amino acid sequence set forth in SEQ ID NO: 31. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0207] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H-V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 15]

[0208] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 16. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 31. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO:24. H and V comprising the amino acid sequence set forth in SEQ ID NO: 31. L SEQ ID NOs: 24 and 31 are provided in Table 16. In certain embodiments, the scFv is designated "k3-h2."

[0209] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H SEQ ID NOs: 12-14 are provided in Table 16.

[0210] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 16.

[0211] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0212] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0213] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 24. H and V comprising the amino acid sequence set forth in SEQ ID NO: 31. L In certain embodiments, V H and V Lare linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0214] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 16]

[0215] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 17. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 31. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 25. H and V comprising the amino acid sequence set forth in SEQ ID NO: 31. L SEQ ID NOs: 25 and 31 are provided in Table 17. In certain embodiments, the scFv is designated "k3-h3."

[0216] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H SEQ ID NOs: 12-14 are provided in Table 17.

[0217] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 17.

[0218] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0219] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0220] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 25. H and V comprising the amino acid sequence set forth in SEQ ID NO: 31. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0221] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 17]

[0222] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 18. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 31. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO:27. H and V comprising the amino acid sequence set forth in SEQ ID NO: 31. LSEQ ID NOs: 27 and 31 are provided in Table 18. In certain embodiments, the scFv is designated "k3-h4."

[0223] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof. H SEQ ID NOs: 12, 13, and 26 are provided in Table 18.

[0224] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 18.

[0225] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0226] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26. Hand a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0227] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO:27. H and V comprising the amino acid sequence set forth in SEQ ID NO: 31. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0228] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 18]

[0229] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 19. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 31. LIn certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO:28. H and V comprising the amino acid sequence set forth in SEQ ID NO: 31. L SEQ ID NOs: 28 and 31 are provided in Table 19. In certain embodiments, the scFv is designated "k3-h5."

[0230] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H SEQ ID NOs: 12-14 are provided in Table 19.

[0231] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 19.

[0232] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0233] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0234] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 28. H and V comprising the amino acid sequence set forth in SEQ ID NO: 31. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0235] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 19]

[0236] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 20. H Area and V LIn certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 31. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO:29. H and V comprising the amino acid sequence set forth in SEQ ID NO: 31. L SEQ ID NOs: 29 and 31 are provided in Table 20. In certain embodiments, the scFv is designated "k3-h6."

[0237] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof. H SEQ ID NOs: 12, 13, and 26 are provided in Table 20.

[0238] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 20.

[0239] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof. Hand a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0240] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0241] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO:29. H and V comprising the amino acid sequence set forth in SEQ ID NO: 31. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0242] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 20]

[0243] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 21. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 32. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 22. H and V comprising the amino acid sequence set forth in SEQ ID NO: 32. L SEQ ID NOs: 22 and 32 are provided in Table 21. In certain embodiments, the scFv is designated "k4-h1."

[0244] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H SEQ ID NOs: 12-14 are provided in Table 21.

[0245] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 21.

[0246] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0247] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0248] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 22. H and V comprising the amino acid sequence set forth in SEQ ID NO: 32. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0249] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 21]

[0250] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 22. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 32. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO:24. H and V comprising the amino acid sequence set forth in SEQ ID NO: 32. L SEQ ID NOs: 24 and 32 are provided in Table 22. In certain embodiments, the scFv is designated "k4-h2."

[0251] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H SEQ ID NOs: 12-14 are provided in Table 22.

[0252] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. LSEQ ID NOs: 15-17 are provided in Table 22.

[0253] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0254] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0255] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 24. H and V comprising the amino acid sequence set forth in SEQ ID NO: 31. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0256] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H-V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 22]

[0257] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 23. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 32. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 25. H and V comprising the amino acid sequence set forth in SEQ ID NO: 32. L SEQ ID NOs: 25 and 23 are provided in Table 23. In certain embodiments, the scFv is designated "k4-h3."

[0258] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H SEQ ID NOs: 12-14 are provided in Table 23.

[0259] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 23.

[0260] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0261] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0262] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 25. H and V comprising the amino acid sequence set forth in SEQ ID NO: 32. L In certain embodiments, V H and V Lare linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0263] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 23]

[0264] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 24. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 32. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO:27. H and V comprising the amino acid sequence set forth in SEQ ID NO: 32. L SEQ ID NOs: 27 and 32 are provided in Table 24. In certain embodiments, the scFv is designated "k4-h4."

[0265] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof. H SEQ ID NOs: 12, 13, and 26 are provided in Table 24.

[0266] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 24.

[0267] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0268] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0269] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO:27. H and V comprising the amino acid sequence set forth in SEQ ID NO: 32. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0270] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 24]

[0271] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 25. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 32. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO:28. H and V comprising the amino acid sequence set forth in SEQ ID NO: 32. LSEQ ID NOs: 28 and 32 are provided in Table 25. In certain embodiments, the scFv is designated "k4-h5."

[0272] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H SEQ ID NOs: 12-14 are provided in Table 25.

[0273] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 25.

[0274] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0275] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14. Hand a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0276] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 28. H and V comprising the amino acid sequence set forth in SEQ ID NO: 32. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0277] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 25]

[0278] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 26. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 32. LIn certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO:29. H and V comprising the amino acid sequence set forth in SEQ ID NO: 32. L SEQ ID NOs: 29 and 32 are provided in Table 26. In certain embodiments, the scFv is designated "k4-h6."

[0279] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof. H SEQ ID NOs: 12, 13, and 26 are provided in Table 26.

[0280] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 26.

[0281] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0282] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0283] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO:29. H and V comprising the amino acid sequence set forth in SEQ ID NO: 32. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0284] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 26]

[0285] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 27. H Area and V LIn certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 19. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 22. H and V comprising the amino acid sequence set forth in SEQ ID NO: 19. L SEQ ID NOs: 22 and 19 are provided in Table 27. In certain embodiments, the scFv is designated "k5-h1."

[0286] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H SEQ ID NOs: 12-14 are provided in Table 27.

[0287] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 27.

[0288] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. Hand a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0289] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0290] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 22. H and V comprising the amino acid sequence set forth in SEQ ID NO: 23. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0291] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 27]

[0292] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 28. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 19. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO:24. H and V comprising the amino acid sequence set forth in SEQ ID NO: 19. L SEQ ID NOs: 24 and 19 are provided in Table 28. In certain embodiments, the scFv is designated "k5-h2."

[0293] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H SEQ ID NOs: 12-14 are provided in Table 28.

[0294] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 28.

[0295] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0296] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0297] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 24. H and V comprising the amino acid sequence set forth in SEQ ID NO: 19. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0298] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 28]

[0299] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 29. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 19. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 25. H and V comprising the amino acid sequence set forth in SEQ ID NO: 19. L SEQ ID NOs: 25 and 19 are provided in Table 29. In certain embodiments, the scFv is designated "k5-h3."

[0300] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H SEQ ID NOs: 12-14 are provided in Table 29.

[0301] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. LSEQ ID NOs: 15-17 are provided in Table 29.

[0302] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0303] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0304] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 25. H and V comprising the amino acid sequence set forth in SEQ ID NO: 19. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0305] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H-V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 29]

[0306] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 30. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 19. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO:27. H and V comprising the amino acid sequence set forth in SEQ ID NO: 19. L SEQ ID NOs: 27 and 19 are provided in Table 30. In certain embodiments, the scFv is designated "k5-h4."

[0307] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof. H SEQ ID NOs: 12, 13, and 26 are provided in Table 30.

[0308] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 30.

[0309] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0310] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0311] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO:27. H and V comprising the amino acid sequence set forth in SEQ ID NO: 19. L In certain embodiments, V H and V Lare linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0312] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 30]

[0313] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 31. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 19. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO:28. H and V comprising the amino acid sequence set forth in SEQ ID NO: 19. L SEQ ID NOs: 28 and 19 are provided in Table 31. In certain embodiments, the scFv is designated "k5-h5."

[0314] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H SEQ ID NOs: 12-14 are provided in Table 31.

[0315] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 31.

[0316] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0317] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0318] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 28. H and V comprising the amino acid sequence set forth in SEQ ID NO: 19. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0319] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 31]

[0320] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 32. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 19. L In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO:29. H and V comprising the amino acid sequence set forth in SEQ ID NO: 19. LSEQ ID NOs: 29 and 19 are provided in Table 32. In certain embodiments, the scFv is designated "k5-h6."

[0321] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof. H SEQ ID NOs: 12, 13, and 26 are provided in Table 32.

[0322] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 32.

[0323] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof. H and a V comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0324] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26. Hand a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes.

[0325] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO:29. H and V comprising the amino acid sequence set forth in SEQ ID NO: 32. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0326] In certain embodiments, the heavy chain variable region (V H ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 32]

[0327] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 33. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 34. LSEQ ID NOs: 33 and 34 are provided in Table 33. In certain embodiments, the scFv is designated "143G03."

[0328] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 33. H and V comprising the amino acid sequence set forth in SEQ ID NO: 34. L Includes:

[0329] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof. H SEQ ID NOs: 12, 13, and 26 are provided in Table 33.

[0330] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L SEQ ID NOs: 15-17 are provided in Table 33.

[0331] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof. H and a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof. L Includes:

[0332] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 17. L Includes:

[0333] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 33. H and V comprising the amino acid sequence set forth in SEQ ID NO: 34. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0334] In certain embodiments, the variable region is a heavy chain variable region (V H ) are located at the N-terminus. In certain embodiments, the variable regions are arranged from the N-terminus to the C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 33]

[0335] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 34. H Area and V LIn certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 42. L SEQ ID NOs: 41 and 42 are provided in Table 34. In certain embodiments, the scFv is designated "04B06."

[0336] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 41. H and V comprising the amino acid sequence set forth in SEQ ID NO: 42. L Includes:

[0337] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 35 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 36 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 37 or a conservative modification thereof. H SEQ ID NOs: 35-37 are provided in Table 34.

[0338] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 38 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 39 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 40 or a conservative modification thereof. L SEQ ID NOs: 38-40 are provided in Table 34.

[0339] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 35 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 36 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 37 or a conservative modification thereof. Hand a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 38 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 39 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 40 or a conservative modification thereof. L Includes:

[0340] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 35, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 36, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 37. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 38, CDR2 having the amino acid sequence set forth in SEQ ID NO: 39, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 40. L Includes:

[0341] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 41. H and V comprising the amino acid sequence set forth in SEQ ID NO: 42. L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0342] In certain embodiments, the variable region is a heavy chain variable region (V H ) are located at the N-terminus. In certain embodiments, the variable regions are arranged from the N-terminus to the C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 34]

[0343] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 35. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 50. L SEQ ID NOs: 49 and 50 are provided in Table 35. In certain embodiments, the scFv is designated "12D10v1."

[0344] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO:49. H and V comprising the amino acid sequence set forth in SEQ ID NO: 50 L Includes:

[0345] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 43 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 44 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 45 or a conservative modification thereof. H SEQ ID NOs: 43-45 are provided in Table 35.

[0346] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 46 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 47 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 48 or a conservative modification thereof. L SEQ ID NOs: 46-48 are provided in Table 35.

[0347] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 43 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 44 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 45 or a conservative modification thereof. H and a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 46 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 47 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 48 or a conservative modification thereof. L Includes:

[0348] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 43, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 44, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 45. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 46, CDR2 having the amino acid sequence set forth in SEQ ID NO: 47, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 48. L Includes:

[0349] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO:49. H and V comprising the amino acid sequence set forth in SEQ ID NO: 50 L In certain embodiments, V H and V L are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0350] In certain embodiments, the variable region is a heavy chain variable region (V H ) are located at the N-terminus. In certain embodiments, the variable regions are arranged from the N-terminus to the C-terminus: V H -V L In certain embodiments, the light chain variable region (VL ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 35]

[0351] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 36. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 53. L SEQ ID NOs: 49 and 53 are provided in Table 36. In certain embodiments, the scFv is designated "12D10v2."

[0352] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO:49. H and V comprising the amino acid sequence set forth in SEQ ID NO: 53. L Includes:

[0353] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 43 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 44 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 45 or a conservative modification thereof. H SEQ ID NOs: 43-45 are provided in Table 36.

[0354] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 51 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 52 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 40 or a conservative modification thereof. L SEQ ID NOs: 40, 51, and 52 are provided in Table 36.

[0355] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 43 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 44 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 45 or a conservative modification thereof. H and a V comprising a CDR1 having the amino acid sequence set forth in SEQ ID NO: 51 or a conservative modification thereof, a CDR2 having the amino acid sequence set forth in SEQ ID NO: 52 or a conservative modification thereof, and a CDR3 having the amino acid sequence set forth in SEQ ID NO: 40 or a conservative modification thereof. L Includes:

[0356] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 43, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 44, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 45. H and a V comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 51, CDR2 having the amino acid sequence set forth in SEQ ID NO: 52, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 40. L Includes:

[0357] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO:49. H and V comprising the amino acid sequence set forth in SEQ ID NO: 53. L In certain embodiments, V H and V Lare linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, or SEQ ID NO: 143.

[0358] In certain embodiments, the variable region is a heavy chain variable region (V H ) are located at the N-terminus. In certain embodiments, the variable regions are arranged from the N-terminus to the C-terminus: V H -V L In certain embodiments, the light chain variable region (V L ) is positioned at the N-terminus. In certain embodiments, the variable region is positioned from N-terminus to C-terminus: V L -V H . [Table 36]

[0359] In certain embodiments, the anti-L1CAM antibody is an scFv, an scFv-Fc fusion protein, or a VFv selected from Table 37. H Area and V L In certain embodiments, the anti-L1CAM scFv is a full-length human IgG (or antibody fragment thereof) having a V domain or CDR. H In certain embodiments, the anti-L1CAM scFv comprises a V comprising the amino acid sequence set forth in SEQ ID NO: 61. L SEQ ID NOs: 60 and 61 are provided in Table 37. In certain embodiments, the scFv is designated "13G04."

[0360] In certain embodiments, the anti-L1CAM scFv comprises the amino acid sequence set forth in SEQ ID NO: 60. H and V comprising the amino acid sequence set forth in SEQ ID NO: 61. L Includes:

[0361] In certain embodiments, the anti-L1CAM scFv comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 54 or a conservative modification thereof, a CDR2 comprising ...

Claims

1. (a) a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 2 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 3 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 4 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 5 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 6 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 7 or a conservative modification thereof; (b) a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof; (c) a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17 or a conservative modification thereof; (d) a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 35 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 36 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 37 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 38 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 39 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 40 or a conservative modification thereof; (e) a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 43 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 44 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 45 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 46 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 47 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 48 or a conservative modification thereof; (f) a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 43 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 44 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 45 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 51 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 52 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 40 or a conservative modification thereof; (g) a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 54 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 55 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 56 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 57 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 58 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 59 or a conservative modification thereof; (h) a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 62 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 63 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 64 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 65 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 58 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 66 or a conservative modification thereof; (i) a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 69 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 71 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 72 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 73 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 74 or a conservative modification thereof; (j) a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 81 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 83 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 84 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 85 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 86 or a conservative modification thereof; (k) a heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 93 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 94 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 95 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 96 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 97 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 98 or a conservative modification thereof; (l) A heavy chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 105 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 106 or a conservative modification thereof, CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 107 or a conservative modification thereof, and a light chain variable region comprising CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 108 or a conservative modification thereof, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 39 or a conservative modification thereof, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 109 or a conservative modification thereof; or (m) An anti-L1CAM antibody or antigen-binding fragment thereof, comprising a heavy chain variable region comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 116 or a conservative modification thereof, CDR2 having the amino acid sequence set forth in SEQ ID NO: 117 or a conservative modification thereof, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 118 or a conservative modification thereof, and a light chain variable region comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 119 or a conservative modification thereof, CDR2 having the amino acid sequence set forth in SEQ ID NO: 120, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 121 or a conservative modification thereof.

2. (a) the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:2, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:3, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:4, and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:5, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:6, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:7; or (b) the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17; or (c) the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26, and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17; or (d) the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 35, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 36, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 37; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 38, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 39, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 40v; (e) the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 43, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 44, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 45; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 46, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 47, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 48; (f) the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 43, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 44, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 45; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 51, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 52, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 40; (g) the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 54, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 55, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 56; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 57, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 59; (h) the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 62, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 63, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 64; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 65, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 66; (i) the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 69, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 71; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 72, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 73, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 74; or (j) the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 81, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 83; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 84, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 85, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 86; (k) the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 93, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 94, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 95; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 96, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 97, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 98; (l) the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 105, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 106, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 107; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 108, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 39, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 109; or (m) The anti-L1CAM antibody or antigen-binding fragment thereof of claim 1, wherein the heavy chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 116, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 117, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 118, and the light chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 119, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 120, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO:

121.

3. (a) the heavy chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO:2, CDR2 comprising the amino acid sequence set forth in SEQ ID NO:3, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO:4, and the light chain variable region comprising CDR1 comprises the amino acid sequence set forth in SEQ ID NO:5, CDR2 comprising the amino acid sequence set forth in SEQ ID NO:6, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO:7; or (b) the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17; or (c) An anti-L1CAM antibody or antigen-binding fragment thereof according to claim 1 or 2, wherein the heavy chain variable region comprises CDR1 having the amino acid sequence set forth in SEQ ID NO: 69, CDR2 having the amino acid sequence set forth in SEQ ID NO: 70, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 71, and the light chain variable region comprises CDR1 having the amino acid sequence set forth in SEQ ID NO: 72, CDR2 having the amino acid sequence set forth in SEQ ID NO: 73, and CDR3 having the amino acid sequence set forth in SEQ ID NO:

74.

4. An anti-L1CAM antibody or antigen-binding fragment thereof according to any one of claims 1 to 3, wherein the heavy chain variable region comprises CDR1 having the amino acid sequence set forth in SEQ ID NO: 2, CDR2 having the amino acid sequence set forth in SEQ ID NO: 3, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 4, and the light chain variable region comprising CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 5, CDR2 having the amino acid sequence set forth in SEQ ID NO: 6, and CDR3 having the amino acid sequence set forth in SEQ ID NO:

7.

5. An anti-L1CAM antibody or antigen-binding fragment thereof according to any one of claims 1 to 3, wherein the heavy chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 13, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 14, and the light chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 15, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO:

17.

6. An anti-L1CAM antibody or antigen-binding fragment thereof according to any one of claims 1 to 3, wherein the heavy chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 69, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 71, and the light chain variable region comprises CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 72, CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 73, and CDR3 comprising the amino acid sequence set forth in SEQ ID NO:

74.

7. (a) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% homologous or identical to the amino acid sequence set forth in SEQ ID NO:8, SEQ ID NO:18, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:33, SEQ ID NO:41, SEQ ID NO:49, SEQ ID NO:60, SEQ ID NO:67, SEQ ID NO:75, SEQ ID NO:87, SEQ ID NO:99, SEQ ID NO:110, SEQ ID NO:122, SEQ ID NO:128, SEQ ID NO:130, SEQ ID NO:134, or SEQ ID NO:135; or (b) The anti-L1CAM antibody or antigen-binding fragment thereof according to any one of claims 1 to 6, comprising a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% homologous or identical to the amino acid sequence set forth in SEQ ID NO:9, SEQ ID NO:19, SEQ ID NO:23, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:42, SEQ ID NO:50, SEQ ID NO:53, SEQ ID NO:61, SEQ ID NO:68, SEQ ID NO:76, SEQ ID NO:88, SEQ ID NO:100, SEQ ID NO:111, SEQ ID NO:123, SEQ ID NO:129, SEQ ID NO:131, SEQ ID NO:132, or SEQ ID NO:

133.

8. (a) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:8, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:9; (b) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 18, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 19; (c) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:22, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:23; (d) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:24, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:23; (e) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:25, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:23; (f) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:27, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:23; (g) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:28, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:23; (h) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:29, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:23; (i) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:22, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:30; (j) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:24, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:30; (k) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:25, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:30; (l) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:27, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:30; (m) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:28, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:30; (n) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:29, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:30; (o) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:22, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:31; (p) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:24, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:31; (q) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:25, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:31; (r) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:27, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:31; (s) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:28, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:31; (t) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:29, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:31; (u) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:22, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:32; (v) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:24, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:32; (w) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:25, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:32; (x) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:27, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:32; (y) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:28, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:32; (z) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:29, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:32; (aa) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:22, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:19; (ab) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:24, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:19; (ac) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:25, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:19; (ad) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:27, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:19; (ae) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:28, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:19; (af) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:29, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:19; (ag) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 33, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 34; (ah) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:41, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:42; (ai) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 49, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 50; (aj) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:49, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:53; (ak) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 60, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 61; (a1) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:67, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:68; (am) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 75, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 76; (an) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 87, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 88; (ao) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 99, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 100; (ap) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 110, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 111; (aq) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 122, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 123; (ar) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 128, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 129; (as) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 130, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 131; (at) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 130, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 132; (au) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 130, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 133; (av) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 134, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 131; (aw) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 134, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 132; (ax) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 134, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 133; (ay) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 135, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 131; (az) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 135, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 132; (ba) a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 135, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 133; and (bb) The anti-L1CAM antibody or antigen-binding fragment thereof according to any one of claims 1 to 7, comprising a heavy chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO: 135, and a light chain variable region comprising an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:

136.

9. (a) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 8 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 9; or (b) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 18 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 19; or (c) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 22 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 23; or (d) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:24 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:23; or (e) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:25 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:23; or (f) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:27 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:23; or (g) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:28 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:23; or (h) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:29 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:23; or (i) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 22 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 30; or (j) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 24 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 30; or (k) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 25 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 30; or (l) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:27 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:30; or (m) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:28 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:30; or (n) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:29 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:30; or (o) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 22 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 31; or (p) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:24 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:31; or (q) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:25, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:31; or (r) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:27 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:31; or (s) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:28 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:31; or (t) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:29 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:31; or (u) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 22 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 32; or (v) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:24 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:32; or (w) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:25 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:32; or (x) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:27 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:32; or (y) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:28 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:32; or (z) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:29 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:32; or (aa) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 22 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 19; or (ab) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 24 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 19; or (ac) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 25 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 19; or (ad) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:27 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:19; or (ae) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:28 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:19; or (af) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:29 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:19; or (ag) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 33 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 34; or (ah) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 41 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 42; or (ai) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 49 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 50; or (aj) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:49 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:53; or (ak) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 60 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 61; or (a1) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 67 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 68; or (am) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 75 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 76; or (an) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 87 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 88; or (ao) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 99 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 100; or (ap) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 110 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 111; or (aq) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 122 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 123; or (ar) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 128 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 129; or (as) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 130 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 131; or (at) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 130 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 132; or (au) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 130 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 133; or (av) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 134 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 131; or (aw) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 134 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 132; or (ax) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 134 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 133; or (ay) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 135 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 131; or (az) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 135 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 132; or (ba) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 135 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 133; or (bb) The antibody or antigen-binding fragment thereof of any one of claims 1 to 8, wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 135 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:

136.

10. The anti-L1CAM antibody or antigen-binding fragment thereof according to any one of claims 1 to 9, wherein the antibody comprises a heavy chain constant region and / or a light chain constant region.

11. (a) the heavy chain constant region comprises an amino acid sequence that is about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% identical to the amino acid sequence set forth in SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, or SEQ ID NO:147; and / or (b) The anti-L1CAM antibody or antigen-binding fragment thereof of claim 10, wherein the light chain constant region comprises an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% identical to the amino acid sequence set forth in SEQ ID NO:

148.

12. (a) the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, or SEQ ID NO: 147; and / or (b) the light chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 148; and (b) the anti-L1CAM antibody or antigen-binding fragment thereof according to claim 10 or 11.

13. The anti-L1CAM antibody or antigen-binding fragment thereof according to any one of claims 1 to 12, wherein the antibody comprises human variable region framework regions.

14. The anti-L1CAM antibody or antigen-binding fragment thereof according to any one of claims 1 to 13, which is fully human or an antigen-binding fragment thereof.

15. The anti-L1CAM antibody or antigen-binding fragment thereof according to any one of claims 1 to 12, which is a chimeric antibody or antigen-binding fragment thereof.

16. The anti-L1CAM antibody or antigen-binding fragment thereof according to any one of claims 1 to 12, which is a humanized antibody or antigen-binding fragment thereof.

17. The antigen-binding fragment may be Fab, Fab', F(ab') ２ 17. The anti-L1CAM antibody or antigen-binding fragment thereof according to any one of claims 1 to 16, which is a variable fragment (Fv), or a single-chain variable region (scFv).

18. 18. The anti-L1CAM antibody or antigen-binding fragment thereof of claim 17, wherein the antigen-binding fragment is an scFv.

19. (a) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 8, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 9; (b) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 18, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 19; (c) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 22, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 23; (d) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 24, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 23; (e) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 25, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 23; (f) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 27, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 23; (g) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 28, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 23; (h) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 29, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 23; (i) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 22, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 30; (j) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 24, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 30; (k) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 25, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 30; (l) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 27, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 30; (m) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:28, and a light chain variable region comprising CDR1, CDR2, and CDR3 of a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:30; (n) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 29, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 30; (o) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 22, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 31; (p) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 24, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 31; (q) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 25, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 31; (r) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:27, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:31; (s) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:28, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:31; (t) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:29, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:31; (u) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 22, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 32; (v) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 24, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 32; (w) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 25, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 32; (x) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 27, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 32; (y) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 28, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 32; (z) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:29, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:32; (aa) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 22, and a light chain variable region comprising CDR1, CDR2, and CDR3 of a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 19; (ab) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 24, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 19; (ac) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 25, and a light chain variable region comprising CDR1, CDR2, and CDR3 of a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 19; (ad) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:27, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:19; (ae) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 28, and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 19; (af) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:29, and a light chain variable region comprising CDR1, CDR2, and CDR3 of a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:19; (ag) the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 33, and the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 34; (ah) the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 41, and the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 42; (ai) the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 49, and the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 50; (aj) the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 49, and the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 53; (ak) the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 60, and the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 61; (a1) the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 67, and the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 68; (am) the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 75, and the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 76; (an) the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 87, and the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 88; (ao) the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 99, and the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 100; (ap) the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 110, and the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 111; (aq) the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 122, and the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 123; (ar) the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 128, and the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 129; (as) the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 130, and the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 131; (at) the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 130, and the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 132; (au) the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 130, and the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 133; (av) the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 134, and the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 131; (aw) the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 134, and the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 132; (ax) the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 134, and the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 133; (ay) the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 135, and the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 131; (az) the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 135, and the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 132; (ba) the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 135, and the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 133; or (bb) An anti-L1CAM antibody or antigen-binding fragment thereof, comprising the heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 135, and the light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:

136.

20. (a) a single chain variable region (scFv) comprising an amino acid sequence that is about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% identical to SEQ ID NO:77 or SEQ ID NO:78; (b) a single chain variable region (scFv) comprising an amino acid sequence that is about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% identical to SEQ ID NO:89 or SEQ ID NO:90; (c) a single chain variable region (scFv) comprising an amino acid sequence that is about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% identical to SEQ ID NO: 101 or SEQ ID NO: 102; (d) a single chain variable region (scFv) comprising an amino acid sequence that is about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% identical to SEQ ID NO: 112 or SEQ ID NO: 113; or (e) An anti-L1CAM antibody or antigen-binding fragment thereof, comprising a single-chain variable region (scFv) comprising an amino acid sequence that is about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% identical to SEQ ID NO: 124 or SEQ ID NO:

125.

21. (a) the scFv comprises the amino acid sequence set forth in SEQ ID NO: 77 or SEQ ID NO: 78; (b) the scFv comprises the amino acid sequence set forth in SEQ ID NO: 89 or SEQ ID NO: 90; (c) the scFv comprises the amino acid sequence set forth in SEQ ID NO: 101 or SEQ ID NO: 102; (d) the scFv comprises the amino acid sequence set forth in SEQ ID NO: 112 or SEQ ID NO: 113; or (e) The anti-L1CAM antibody or antigen-binding fragment thereof of claim 20, wherein the scFv comprises the amino acid sequence set forth in SEQ ID NO: 124 or SEQ ID NO:

125.

22. An anti-L1CAM antibody or antigen-binding fragment thereof, comprising a heavy chain variable region comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 2, CDR2 having the amino acid sequence set forth in SEQ ID NO: 3, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 4, and a light chain variable region comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 5, CDR2 having the amino acid sequence set forth in SEQ ID NO: 6, and CDR3 having the amino acid sequence set forth in SEQ ID NO:

7.

23. An anti-L1CAM antibody or antigen-binding fragment thereof, comprising a heavy chain variable region comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 12, CDR2 having the amino acid sequence set forth in SEQ ID NO: 13, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 14, and a light chain variable region comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 15, CDR2 having the amino acid sequence set forth in SEQ ID NO: 16, and CDR3 having the amino acid sequence set forth in SEQ ID NO:

17.

24. An anti-L1CAM antibody or antigen-binding fragment thereof, comprising a heavy chain variable region comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 69, CDR2 having the amino acid sequence set forth in SEQ ID NO: 70, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 71, and a light chain variable region comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 72, CDR2 having the amino acid sequence set forth in SEQ ID NO: 73, and CDR3 having the amino acid sequence set forth in SEQ ID NO:

74.

25. An anti-L1CAM antibody or antigen-binding fragment thereof, comprising a heavy chain variable region comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 81, CDR2 having the amino acid sequence set forth in SEQ ID NO: 82, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 83, and a light chain variable region comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 84, CDR2 having the amino acid sequence set forth in SEQ ID NO: 85, and CDR3 having the amino acid sequence set forth in SEQ ID NO:

86.

26. An anti-L1CAM antibody or antigen-binding fragment thereof, comprising a heavy chain variable region comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 93, CDR2 having the amino acid sequence set forth in SEQ ID NO: 94, and CDR3 having the amino acid sequence set forth in SEQ ID NO: 95, and a light chain variable region comprising CDR1 having the amino acid sequence set forth in SEQ ID NO: 96, CDR2 having the amino acid sequence set forth in SEQ ID NO: 97, and CDR3 having the amino acid sequence set forth in SEQ ID NO:

98.

27. An anti-L1CAM antibody or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:8, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:

9.

28. An anti-L1CAM antibody or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 18, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:

19.

29. An anti-L1CAM antibody or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 75, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:

76.

30. An anti-L1CAM antibody or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 87, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:

88.

31. An anti-L1CAM antibody or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 99, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:

100.

32. An anti-L1CAM antibody or antigen-binding fragment thereof, comprising an scFv comprising the amino acid sequence set forth in SEQ ID NO: 77 or SEQ ID NO:

78.

33. An anti-L1CAM antibody or antigen-binding fragment thereof, comprising an scFv comprising the amino acid sequence set forth in SEQ ID NO: 89 or SEQ ID NO:

90.

34. An anti-L1CAM antibody or antigen-binding fragment thereof, comprising an scFv comprising the amino acid sequence set forth in SEQ ID NO: 101 or SEQ ID NO:

102.

35. An antibody or antigen-binding fragment thereof that cross-competes with the anti-L1CAM antibody or antigen-binding fragment thereof of any one of claims 1 to 34 for binding to L1CAM.

36. An antibody or antigen-binding fragment thereof that binds to the same epitope region on L1CAM as the anti-L1CAM antibody or antigen-binding fragment thereof according to any one of claims 1 to 34.

37. A composition comprising an anti-L1CAM antibody or antigen-binding fragment thereof according to any one of claims 1 to 36.

38. 38. The composition of claim 37, which is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier.

39. An immunoconjugate comprising the anti-L1CAM antibody or antigen-binding fragment thereof of any one of claims 1 to 36, linked to a therapeutic agent.

40. 40. The immunoconjugate of claim 39, wherein the therapeutic agent is a drug, a cytotoxin, or a radioisotope.

41. 41. The immunoconjugate of claim 39 or 40, wherein the therapeutic agent is a compound selected from the group consisting of dolastatin, maytansinoid, duocarmycin, anthracycline, camptothecin, and amatoxin.

42. 42. The immunoconjugate of claim 41, wherein the therapeutic agent is selected from the group consisting of monomethyl auristatin E, ABZ038, duocarmycin™, PNU159682, SN38, and α-amanitin.

43. 43. The immunoconjugate of claim 41 or 42, wherein the therapeutic agent is PNU159682.

44. The immunoconjugate of any one of claims 39 to 43, comprising a linker.

45. 45. The immunoconjugate of claim 44, wherein the linker is a cleavable linker or a non-cleavable linker.

46. 46. ​​The immunoconjugate of any one of claims 39 to 45, comprising a molecule of the following formula: 【Chemistry 9】

47. 47. The immunoconjugate of any one of claims 39 to 46, comprising a molecule of the following formula: 【Chemistry 10】

48. A composition comprising the immunoconjugate of any one of claims 39 to 47.

49. 49. The composition of claim 48, which is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier.

50. A multispecific molecule comprising an antibody or antigen-binding fragment thereof according to any one of claims 1 to 36 linked to one or more functional moieties.

51. 51. The multispecific molecule of claim 50, wherein the one or more functional moieties have a binding specificity different from that of the antibody or antigen-binding fragment thereof.

52. 52. A composition comprising the multispecific molecule of claim 50 or 51.

53. 53. The composition of claim 52, which is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier.

54. A nucleic acid encoding the antibody or antigen-binding fragment thereof according to any one of claims 1 to 36.

55. A nucleic acid encoding the heavy chain variable region of the antibody or antigen-binding fragment thereof according to any one of claims 1 to 36.

56. A nucleic acid encoding the light chain variable region of the antibody or antigen-binding fragment thereof according to any one of claims 1 to 36.

57. A vector comprising the nucleic acid of any one of claims 54 to 56.

58. 58. A host cell comprising the vector of claim 57.

59. 1. A method for detecting L1CAM in a whole cell, tissue, or blood sample, comprising: (a) contacting a cell, tissue, or blood sample with the antibody or antigen-binding fragment thereof of any one of claims 1 to 36, wherein the antibody or antigen-binding fragment thereof comprises a detectable label; (b) determining the amount of labeled antibody or antigen-binding fragment thereof bound to the cells, tissue, or blood sample by measuring the amount of detectable label associated with the cells or tissue, wherein the amount of bound antibody or antigen-binding fragment thereof indicates the amount of L1CAM in the cells, tissue, or blood sample.

60. 52. A method of treating or ameliorating a disease or disorder associated with L1CAM in a subject, comprising administering to the subject an antibody or antigen-binding fragment thereof of any one of claims 1 to 36, an immunoconjugate of any one of claims 39 to 47, a multispecific molecule of claim 50 or 51, or a composition of any one of claims 37, 38, 48, 49, 52, or 53.

61. 61. The method of claim 60, wherein the disease or disorder is a tumor.

62. 52. A method of reducing tumor burden in a subject, comprising administering to the subject an antibody or antigen-binding fragment thereof of any one of claims 1 to 36, an immunoconjugate of any one of claims 39 to 47, a multispecific molecule of claim 50 or 51, or a composition of any one of claims 37, 38, 48, 49, 52, or 53.

63. 63. The method of claim 62, wherein the method reduces the number of tumor cells, reduces tumor size, and / or eradicates tumors in the subject.

64. 52. A method of treating and / or preventing a tumor in a subject, comprising administering to the subject an antibody or antigen-binding fragment thereof of any one of claims 1 to 36, an immunoconjugate of any one of claims 39 to 47, a multispecific molecule of claim 50 or 51, or a composition of any one of claims 37, 38, 48, 49, 52, or 53.

65. 52. A method of increasing or prolonging the survival of a subject bearing a tumor, comprising administering to said subject an antibody or antigen-binding fragment thereof of any one of claims 1 to 36, an immunoconjugate of any one of claims 39 to 47, a multispecific molecule of claim 50 or 51, or a composition of any one of claims 37, 38, 48, 49, 52 or 53.

66. 66. The method of claim 65, wherein said method reduces or eradicates tumor burden in said subject.

67. 67. The method of any one of claims 60 to 66, wherein the tumor is cancer.

68. 68. The method of any one of claims 60 to 67, wherein the tumor is a metastatic cancer.

69. 69. The method of claim 68, wherein the metastatic cancer is an advanced metastatic cancer.

70. 70. The method of any one of claims 60 to 69, wherein the subject is a human.

71. 52. A kit for treating or ameliorating a disease or disorder in a subject, for reducing tumor burden in a subject, for treating and / or preventing a tumor in a subject, and / or for increasing or prolonging survival of a tumor-bearing subject, comprising an antibody or antigen-binding fragment thereof of any one of claims 1 to 36, an immunoconjugate of any one of claims 39 to 47, a multispecific molecule of claim 50 or 51, or a composition of any one of claims 37, 38, 48, 49, 52, or 53.

72. 72. The kit of claim 71, wherein the kit further comprises written instructions for using the antibody or antigen-binding fragment thereof, immunoconjugate, multispecific molecule, or composition to treat or ameliorate a disease or disorder in a subject, to reduce tumor burden in a subject, to treat and / or prevent a tumor in a subject, and / or to increase or prolong survival of a subject with a tumor.

73. 52. The antibody or antigen-binding fragment thereof of any one of claims 1 to 36, the immunoconjugate of any one of claims 39 to 47, the multispecific molecule of claim 50 or 51, or the composition of any one of claims 37, 38, 48, 49, 52 or 53 for use in treating or ameliorating a disease or disorder in a subject, reducing tumor burden in a subject, treating and / or preventing a tumor in a subject, and / or increasing or prolonging survival of a tumor-bearing subject.

74. 54. The antibody or antigen-binding fragment thereof of any one of claims 1 to 36, the immunoconjugate of any one of claims 39 to 47, the multispecific molecule of claim 50 or 51, or the composition of any one of claims 37, 38, 48, 49, 52 or 53 for treating or ameliorating a disease or disorder in a subject, for reducing tumor burden in a subject, for treating and / or preventing a tumor in a subject, and / or for increasing or prolonging survival of a tumor-bearing subject.

75. 52. Use of the antibody or antigen-binding fragment thereof of any one of claims 1 to 36, the immunoconjugate of any one of claims 39 to 47, the multispecific molecule of claim 50 or 51, or the composition of any one of claims 37, 38, 48, 49, 52 or 53 for the manufacture of a medicament for treating or ameliorating a disease or disorder in a subject, for reducing tumor burden in a subject, for treating and / or preventing a tumor in a subject, and / or for increasing or prolonging survival of a tumor-bearing subject.

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