Antibody targeting receptor tyrosine kinase-like orphan receptor 1 and use thereof

Abstract

Provided are an antibody targeting receptor tyrosine kinase-like orphan receptor 1 and a use thereof. Further provided is a pharmaceutical composition comprising the antibody and a use thereof. The provided antibody achieves excellent anti-tumor activity and / or good safety. The provided antibody can be used for the treatment of tumors.

Description

Antibodies targeting receptor tyrosine kinase-like orphan receptor 1 and their applications Technical Field

[0001] The present disclosure belongs to the field of biotechnology, and particularly relates to an antibody or an antigen-binding fragment thereof targeting receptor tyrosine kinase-like orphan receptor 1, and also relates to applications of the antibody or the antigen-binding fragment thereof. Background Art

[0002] Receptor tyrosine kinase-like orphan receptor 1 (ROR1) belongs to the ROR receptor family, a family of tight junction proteins. This family consists of two closely related type I transmembrane proteins, ROR1 and ROR2, that participate in intercellular and intracellular signaling, regulating cell proliferation, differentiation, and metastasis. The structure of ROR1 consists of an extracellular domain, a transmembrane region, and an intracellular region. The extracellular region is composed of an Ig-like domain, a cysteine-rich coiled coil domain, and a kringle domain. The intracellular region is composed of a tyrosine kinase domain, a serine / threonine-rich region, and a proline-rich region.

[0003] ROR1 is selectively overexpressed in many solid and hematologic malignancies, such as leukemia, breast cancer, ovarian cancer, and lung adenocarcinoma, while not significantly expressed in normal adult tissues. Multiple studies have demonstrated that ROR1 can promote tumor growth in vitro and in vivo and plays a role in promoting tumor malignant progression, making ROR1 a potential target for cancer therapy.

[0004] There are some antibodies targeting ROR1 under development, but they are still limited, and more antibodies targeting ROR1 are still needed clinically.

[0005] Summary of the Invention

[0006] The present disclosure provides anti-ROR1 antibodies and antigen-binding fragments thereof, as well as related nucleic acids, vectors, cells, pharmaceutical compositions, preparation methods, and uses encoding the provided antibodies and antigen-binding fragments thereof.

[0007] In one aspect, the present disclosure provides an anti-ROR1 antibody or an antigen-binding fragment thereof comprising:

[0008] (1) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 1, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 2, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 3, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 4, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 5, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 6;

[0009] (2) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 9, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 50, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 11, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 14;

[0010] (3) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 9, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 10, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 11, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 14;

[0011] (4) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 9, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 49, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 11, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 14;

[0012] (5) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 18, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 19, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 22; or

[0013] (6) HCDR1 comprising the amino acid sequence of SEQ ID NO: 25, HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, HCDR3 comprising the amino acid sequence of SEQ ID NO: 27, LCDR1 comprising the amino acid sequence of SEQ ID NO: 28, LCDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 30.

[0014] In one aspect, the present disclosure provides an anti-ROR1 antibody or an antigen-binding fragment thereof comprising:

[0015] (1) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region as shown in SEQ ID NO: 7, and LCDR1, LCDR2, and LCDR3 in the light chain variable region as shown in SEQ ID NO: 8;

[0016] (2) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region as shown in SEQ ID NO: 15, and LCDR1, LCDR2, and LCDR3 in the light chain variable region as shown in SEQ ID NO: 16;

[0017] (3) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region as shown in SEQ ID NO: 23, and LCDR1, LCDR2, and LCDR3 in the light chain variable region as shown in SEQ ID NO: 24;

[0018] (4) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region as shown in SEQ ID NO: 31, and LCDR1, LCDR2, and LCDR3 in the light chain variable region as shown in SEQ ID NO: 32;

[0019] (5) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region as shown in SEQ ID NO: 51, and LCDR1, LCDR2, and LCDR3 in the light chain variable region as shown in SEQ ID NO: 53;

[0020] (6) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region as shown in SEQ ID NO: 51, and LCDR1, LCDR2, and LCDR3 in the light chain variable region as shown in SEQ ID NO: 54;

[0021] (7) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region as shown in SEQ ID NO: 51, and LCDR1, LCDR2, and LCDR3 in the light chain variable region as shown in SEQ ID NO: 55;

[0022] (8) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region as shown in SEQ ID NO: 52, and LCDR1, LCDR2, and LCDR3 in the light chain variable region as shown in SEQ ID NO: 53;

[0023] (9) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having an amino acid sequence as shown in SEQ ID NO: 52, and LCDR1, LCDR2, and LCDR3 in the light chain variable region having an amino acid sequence as shown in SEQ ID NO: 54;

[0024] (10) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region represented by the amino acid sequence of SEQ ID NO: 52, and LCDR1, LCDR2, and LCDR3 in the light chain variable region represented by the amino acid sequence of SEQ ID NO: 55;

[0025] (11) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region represented by the amino acid sequence of SEQ ID NO: 56, and LCDR1, LCDR2, and LCDR3 in the light chain variable region represented by the amino acid sequence of SEQ ID NO: 59;

[0026] (12) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region represented by the amino acid sequence of SEQ ID NO: 57, and LCDR1, LCDR2, and LCDR3 in the light chain variable region represented by the amino acid sequence of SEQ ID NO: 59;

[0027] (13) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region represented by the amino acid sequence of SEQ ID NO: 58, and LCDR1, LCDR2, and LCDR3 in the light chain variable region represented by the amino acid sequence of SEQ ID NO: 59;

[0028] (14) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having an amino acid sequence as shown in SEQ ID NO: 60, and LCDR1, LCDR2, and LCDR3 in the light chain variable region having an amino acid sequence as shown in SEQ ID NO: 62;

[0029] (15) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region represented by the amino acid sequence of SEQ ID NO: 60, and LCDR1, LCDR2, and LCDR3 in the light chain variable region represented by the amino acid sequence of SEQ ID NO: 63;

[0030] (16) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region whose amino acid sequences are as shown in SEQ ID NO: 60, and LCDR1, LCDR2, and LCDR3 in the light chain variable region whose amino acid sequences are as shown in SEQ ID NO: 64;

[0031] (17) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region whose amino acid sequences are as shown in SEQ ID NO: 61, and LCDR1, LCDR2, and LCDR3 in the light chain variable region whose amino acid sequences are as shown in SEQ ID NO: 62;

[0032] (18) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region of the amino acid sequence shown in SEQ ID NO: 61, and LCDR1, LCDR2, and LCDR3 in the light chain variable region of the amino acid sequence shown in SEQ ID NO: 63; or

[0033] (19) HCDR1, HCDR2 and HCDR3 in the heavy chain variable region whose amino acid sequences are as shown in SEQ ID NO: 61, and LCDR1, LCDR2 and LCDR3 in the light chain variable region whose amino acid sequences are as shown in SEQ ID NO: 64.

[0034] In one aspect, the present disclosure provides an isolated nucleic acid comprising a nucleotide sequence encoding an anti-ROR1 antibody or antigen-binding fragment thereof according to the present disclosure.

[0035] In one aspect, the present disclosure provides a vector comprising a nucleic acid described herein.

[0036] In one aspect, the present disclosure provides a host cell comprising the nucleic acid or the vector described in the present disclosure.

[0037] In one aspect, the present disclosure provides an antibody drug conjugate comprising an anti-ROR1 antibody or antigen-binding fragment thereof of the present disclosure.

[0038] In one aspect, the present disclosure provides an anti-ROR1 chimeric antigen receptor comprising an anti-ROR1 antibody or antigen-binding fragment thereof of the present disclosure.

[0039] In one aspect, the present disclosure provides engineered immune effector cells comprising the chimeric antigen receptor of the present disclosure.

[0040] On the other hand, the present disclosure provides a method for preparing the anti-ROR1 antibody or antigen-binding fragment thereof described in the present disclosure, which comprises culturing the host cell to express the ROR1 antibody or antigen-binding fragment thereof, and isolating and purifying the anti-ROR1 antibody or antigen-binding fragment thereof in the system.

[0041] In another aspect, the present disclosure provides a pharmaceutical composition comprising the anti-ROR1 antibody or antigen-binding fragment thereof, the fusion protein, the antibody-drug conjugate or the engineered immune effector cell, and a pharmaceutically acceptable excipient.

[0042] In another aspect, the present disclosure provides use of the anti-ROR1 antibody or antigen-binding fragment thereof, the fusion protein, the antibody-drug conjugate, the engineered immune effector cell, or the pharmaceutical composition in the preparation of a medicament for treating a disease expressing ROR1.

[0043] In another aspect, the present disclosure provides a method for treating a disease expressing ROR1, comprising administering to a subject in need thereof the anti-ROR1 antibody or its antigen-binding fragment, the antibody-drug conjugate, the engineered immune effector cell, or the pharmaceutical composition. In another aspect, the present disclosure provides a method for treating a disease expressing ROR1, comprising administering to a subject in need thereof a therapeutically effective amount of the anti-ROR1 antibody or its antigen-binding fragment, the antibody-drug conjugate, the engineered immune effector cell, or the pharmaceutical composition.

[0044] The anti-ROR1 antibodies or antigen-binding fragments thereof provided by the present disclosure exhibit good anti-tumor effects and / or safety. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] Figures 1A-1C are FACS binding curves of anti-ROR1 chimeric antibodies to ROR1-expressing cells, wherein Figure 1A is A549 cells, Figure 1B is Jeko-1 cells, and Figure 1C is SW620 cells;

[0046] Figures 2A-2I are FACS binding curves of anti-ROR1 humanized antibodies to ROR1-expressing cells, wherein Figures 2A, 2D, and 2G are PA-1 cells, Figures 2B, 2E, and 2H are Jeko-1 cells, and Figures 2C, 2F, and 2I are SW620 cells;

[0047] Figures 3A-3C are FACS assays for the internalization of anti-ROR1 humanized antibodies in ROR1-expressing cells, wherein Figure 3A is for NCI-H1993-ROR1 cells, Figure 3B is for MDA-MB-468-ROR1 cells, and Figure 3C is for NCI-H1975-ROR1 cells;

[0048] FIG4 shows the inhibition rate of the non-canonical Wnt signaling pathway stimulated by Wnt5a in 293T-ROR1-NF-κB cells by anti-ROR1 humanized antibodies;

[0049] FIG5 shows the ADCC effect of anti-ROR1 humanized antibody on PA-1 cells.

[0050] Detailed Description of the Invention

[0051] Definition and Explanation

[0052] Unless otherwise indicated, the following terms used in this disclosure have the following meanings. A particular term should not be construed as undefined or unclear unless specifically defined, but rather should be understood according to its ordinary meaning in the art. When a trade name appears herein, it is intended to refer to the corresponding commercial product or its active ingredient.

[0053] The term "antibody" is used in the broadest sense to cover natural antibodies and artificial antibodies of various structures, including but not limited to monoclonal antibodies, polyclonal antibodies, monospecific antibodies and multispecific antibodies (e.g., bispecific antibodies, trispecific antibodies), and various antibody structures of single-chain antibodies, so long as they exhibit the desired antigen-binding activity.

[0054] The term "antigen-binding fragment" refers to one or more fragments of an antibody that retain the function of specifically binding to an antigen. Examples encompassed by the term "antigen-binding fragment" include: (i) Fab fragments: consisting of V L 、V H (ii) a F(ab')2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) an Fd fragment consisting of the VH and CH1 domains; (iv) an Fv fragment consisting of the VL and VH domains of a single arm of an antibody; (v) a dAb fragment consisting of the VH domain (see Ward et al., Nature. 341:544-546 (1989)); (vi) isolated complementarity determining regions (CDRs); (vii) nanobodies; and single-chain Fv (scFv).

[0055] The term "variable domain" or "variable region" refers to the domain of an antibody that is involved in binding the antibody to the antigen. For example, a natural four-chain antibody (e.g., derived from humans, mice, etc.) has a heavy chain variable region (also referred to as a heavy chain variable domain, VH or VH domain) and a light chain variable region (also referred to as a light chain variable domain, VL or VL domain). In most cases, each variable domain of a natural antibody is essentially composed of four "framework regions (FR)" and three "complementarity determining regions (CDRs)." The four framework regions are respectively referred to as framework region 1 (or FR1), framework region 2 (or FR2), framework region 3 (or FR3), and framework region 4 (or FR4); the framework regions are separated by three complementary determining regions, which are respectively referred to in the art and hereinafter as complementary determining region 1 (or CDR1), complementary determining region 2 (or CDR2), and complementary determining region 3 (or CDR3). Therefore, the general structure of a variable domain can be represented as follows: FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4. The variable domain confers specificity to the antibody for the antigen by providing the antigen-binding site.

[0056] The term "complementarity determining region" (CDR), also known as "hypervariable region" (HVR). Natural four-chain antibodies usually contain six CDRs, three in the heavy chain variable region, namely heavy chain CDR1 (HCDR1), heavy chain CDR2 (HCDR2) and heavy chain CDR3 (HCDR3); and three in the light chain variable region, namely light chain CDR1 (LCDR1), light chain CDR2 (LCDR2) and light chain CDR3 (LCDR3).

[0057] There are many methods to define CDRs. Among them, the Kabat definition is based on sequence variability to divide CDRs and is the most commonly used (Elvin A. Kabat, et al, Sequences of Proteins of Immunological Interest, 5th Edition, Public Health Service, National Institutes of Health, Bethesda, Md. (1991)); while the Chothia definition is based on the position of the structural loop (Cyrus Chothia, et al, Canonical Structures for the Hypervariable Regions of Immunoglobulins, J. Mol. Biol. 196: 901-917 (1987)). The AbM definition is a compromise between the Kabat definition and the Chothia definition and is used by Oxford Molecular's AbM antibody modeling software. The basis of the "contact" definition of CDRs is the analysis of available complex crystal structures. In addition, there are definitions such as IMGT and CCG. However, it should be noted that the boundaries of the CDRs of the same antibody variable region obtained by different demarcation methods may vary, that is, the CDR sequences of the same antibody variable region defined by different demarcation methods may be different. Therefore, when referring to antibodies defined by specific CDR sequences, the scope of the antibodies also covers antibodies defined by CDR sequences of any other definitions (e.g., one or a combination of the Kabat, IMGT, Chothia, Contact, AbM, CCG, etc.).

[0058] The term "treating" means administering a compound (e.g., an antibody) or pharmaceutical composition of the present disclosure to prevent, ameliorate, or eliminate a disease or one or more symptoms associated with the disease, and includes, but is not limited to: (i) preventing the disease or disease state from occurring in a mammal, particularly when such mammal is susceptible to the disease state but has not yet been diagnosed as having the disease state; (ii) inhibiting the disease or disease state, i.e., curbing its development; (iii) relieving the disease or disease state, i.e., causing the disease or disease state to regress; and (iv) reducing any direct or indirect pathological consequences of the disease or disease state.

[0059] The term "therapeutically effective amount" means an amount of a compound of the present disclosure that (i) treats or prevents a specific disease, condition, or disorder, (ii) alleviates, ameliorates, or eliminates one or more symptoms of a specific disease, condition, or disorder, or (iii) prevents or delays the onset of one or more symptoms of a specific disease, condition, or disorder described herein. The amount of an anti-ROR1 antibody or antigen-binding fragment thereof, antibody drug conjugate, engineered immune effector cell, fusion protein, or pharmaceutical composition of the present disclosure that constitutes a "therapeutically effective amount" may vary depending on factors such as the compound or pharmaceutical composition and its ability to elicit a desired response in an individual, the disease state and its severity, the route of administration, and the age, sex, and weight of the mammal to be treated. A therapeutically effective amount can also be routinely determined by one skilled in the art based on their own knowledge and the present disclosure.

[0060] The term "pharmaceutically acceptable" refers to those compounds, materials, compositions and / or dosage forms that are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and animals without excessive toxicity, irritation, allergic response or other problems or complications, commensurate with a reasonable benefit / risk ratio.

[0061] The term "excipient" refers to any ingredient other than the active ingredient (e.g., an antibody of the present disclosure). The choice of excipient will largely depend on factors such as the specific mode of administration, the efficacy of the excipient on solubility and stability, and the nature of the dosage form.

[0062] The term "isolated" refers to a compound of interest, such as an antibody or antigen-binding fragment thereof, or a nucleic acid, that has been separated from its natural environment.

[0063] The term "X n " is equivalent to "Xaa" and refers to unspecified amino acids, and its scope is specified by the subsequent definitions in the relevant expressions.

[0064] As used herein, the term "EC 50 ", also known as half-maximal effective concentration, refers to the concentration of the antibody when the response induced is 50% of the maximum response, that is, halfway between the maximum response and the baseline. EC 50 Measurement can be performed by ELISA or FACS analysis or any other method known in the art.

[0065] “K D ” refers to the equilibrium dissociation constant, which is obtained from the dissociation rate constant (k d ) than the binding rate constant (k a )(i.e., k d / k a) and expressed as molar concentration (M). D The K value can be determined using methods well established in the art. D A preferred method is by using surface plasmon resonance (SPR) technology, preferably using a biosensor system such as Surface plasmon resonance system analysis.

[0066] The term "identity" is also known as consistency. The "percentage (%) identity" of an amino acid sequence refers to the percentage of amino acid residues in the sequence to be aligned that are identical to the amino acid residues in the specific amino acid sequence shown in this article, after comparing the sequence to be aligned and, if necessary, introducing gaps to achieve maximum sequence identity, and not considering any conservative substitutions as part of sequence identity. The alignment of amino acid sequences for identity can be performed in a variety of ways within the scope of the art, such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. Those skilled in the art can determine the appropriate parameters for aligning sequences, including any algorithm needed to obtain maximum alignment over the full length of the comparison sequence.

[0067] The term "subject" includes any human or non-human animal. The term "non-human animal" includes all vertebrates, e.g., mammals and non-mammals, such as non-human primates, sheep, dogs, cats, horses, cows, chickens, amphibians, reptiles, etc. Preferably, the subject according to the present disclosure is a human. Unless otherwise indicated, the terms "patient" or "subject" can be used interchangeably. "Subjects in need thereof" include those who already have a disease or condition, those who are at risk of developing a disease or condition, and those who may develop a disease or condition and for which the purpose is to prevent, delay, or attenuate the disease or condition.

[0068] As used herein, "about" 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 1 or more than 1 standard deviation as practiced in the art. Alternatively, "about" can mean a range of up to ±5%, such as fluctuations within ±2%, ±1%, or ±0.5% of the specific numerical range given. When a specific value is given in the scope of the present disclosure, unless otherwise indicated, the meaning of "about" should be considered to be within an acceptable error range for that specific value. In this document, unless otherwise indicated, the value of a step parameter or condition is modified by "about" by default.

[0069] The terms "comprise," "comprises," or "comprising" and their equivalents (for example, contain, contains, containing, include, includes, and including) should be understood as "including but not limited to," meaning that in addition to the listed elements, components, and steps, other unspecified elements, components, and steps may also be included.

[0070] Herein, singular terms encompass plural referents and vice versa unless the context clearly dictates otherwise.

[0071] Anti-ROR1 antibody or antigen-binding fragment thereof

[0072] The present disclosure provides an anti-ROR1 antibody or an antigen-binding fragment thereof, comprising: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 1, 9, 17 or 25, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 2, 10, 18, 26, 49 or 50, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 3, 11, 19 or 27, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 4, 12, 20 or 28, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 5, 13, 21 or 29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 6, 14, 22 or 30.

[0073] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 1, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 2, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 3, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 4, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 5, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 6.

[0074] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 9, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 50, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 11, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 14; wherein X1 is selected from S or A, X2 is selected from A or Q, and X3 is selected from K or Q. In some specific embodiments, X1 is S, X2 is A, and X3 is K. In some specific embodiments, X1 is A, X2 is Q, and X3 is Q.

[0075] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO:9, a HCDR2 comprising the amino acid sequence of SEQ ID NO:10, a HCDR3 comprising the amino acid sequence of SEQ ID NO:11, a LCDR1 comprising the amino acid sequence of SEQ ID NO:12, a LCDR2 comprising the amino acid sequence of SEQ ID NO:13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:14.

[0076] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO:9, a HCDR2 comprising the amino acid sequence of SEQ ID NO:49, a HCDR3 comprising the amino acid sequence of SEQ ID NO:11, a LCDR1 comprising the amino acid sequence of SEQ ID NO:12, a LCDR2 comprising the amino acid sequence of SEQ ID NO:13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:14.

[0077] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 18, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 19, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 22.

[0078] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 25, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 27, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 28, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 30.

[0079] The present disclosure also provides an anti-ROR1 antibody or an antigen-binding fragment thereof, comprising: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in the amino acid sequence of SEQ ID NO: 7, 15, 23, 31, 51, 52, 56, 57, 58, 60 or 61, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in the amino acid sequence of SEQ ID NO: 8, 16, 24, 32, 53, 54, 55, 59, 62, 63 or 64.

[0080] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region with the amino acid sequence shown in SEQ ID NO:7, and LCDR1, LCDR2 and LCDR3 in the light chain variable region with the amino acid sequence shown in SEQ ID NO:8.

[0081] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region with the amino acid sequence shown in SEQ ID NO: 15, and LCDR1, LCDR2 and LCDR3 in the light chain variable region with the amino acid sequence shown in SEQ ID NO: 16.

[0082] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region with the amino acid sequence shown in SEQ ID NO: 23, and LCDR1, LCDR2 and LCDR3 in the light chain variable region with the amino acid sequence shown in SEQ ID NO: 24.

[0083] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region with the amino acid sequence shown in SEQ ID NO:31, and LCDR1, LCDR2 and LCDR3 in the light chain variable region with the amino acid sequence shown in SEQ ID NO:32.

[0084] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region with the amino acid sequence shown in SEQ ID NO:51, and LCDR1, LCDR2 and LCDR3 in the light chain variable region with the amino acid sequence shown in SEQ ID NO:53.

[0085] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region with the amino acid sequence shown in SEQ ID NO:51, and LCDR1, LCDR2 and LCDR3 in the light chain variable region with the amino acid sequence shown in SEQ ID NO:54.

[0086] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region with the amino acid sequence shown in SEQ ID NO:51, and LCDR1, LCDR2 and LCDR3 in the light chain variable region with the amino acid sequence shown in SEQ ID NO:55.

[0087] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region with the amino acid sequence shown in SEQ ID NO: 52, and LCDR1, LCDR2 and LCDR3 in the light chain variable region with the amino acid sequence shown in SEQ ID NO: 53.

[0088] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region with the amino acid sequence shown in SEQ ID NO: 52, and LCDR1, LCDR2 and LCDR3 in the light chain variable region with the amino acid sequence shown in SEQ ID NO: 54.

[0089] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region with the amino acid sequence shown in SEQ ID NO: 52, and LCDR1, LCDR2 and LCDR3 in the light chain variable region with the amino acid sequence shown in SEQ ID NO: 55.

[0090] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region with the amino acid sequence shown in SEQ ID NO: 56, and LCDR1, LCDR2 and LCDR3 in the light chain variable region with the amino acid sequence shown in SEQ ID NO: 59.

[0091] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region with the amino acid sequence shown in SEQ ID NO: 57, and LCDR1, LCDR2 and LCDR3 in the light chain variable region with the amino acid sequence shown in SEQ ID NO: 59.

[0092] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region with the amino acid sequence shown in SEQ ID NO: 58, and LCDR1, LCDR2 and LCDR3 in the light chain variable region with the amino acid sequence shown in SEQ ID NO: 59.

[0093] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region with the amino acid sequence shown in SEQ ID NO:60, and LCDR1, LCDR2 and LCDR3 in the light chain variable region with the amino acid sequence shown in SEQ ID NO:62.

[0094] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region with the amino acid sequence shown in SEQ ID NO:60, and LCDR1, LCDR2 and LCDR3 in the light chain variable region with the amino acid sequence shown in SEQ ID NO:63.

[0095] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region with the amino acid sequence shown in SEQ ID NO:60, and LCDR1, LCDR2 and LCDR3 in the light chain variable region with the amino acid sequence shown in SEQ ID NO:64.

[0096] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region with the amino acid sequence shown in SEQ ID NO:61, and LCDR1, LCDR2 and LCDR3 in the light chain variable region with the amino acid sequence shown in SEQ ID NO:62.

[0097] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region with the amino acid sequence shown in SEQ ID NO:61, and LCDR1, LCDR2 and LCDR3 in the light chain variable region with the amino acid sequence shown in SEQ ID NO:63.

[0098] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region with the amino acid sequence shown in SEQ ID NO:61, and LCDR1, LCDR2 and LCDR3 in the light chain variable region with the amino acid sequence shown in SEQ ID NO:64.

[0099] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 7, 15, 23, 31, 51, 52, 56, 57, 58, 60, or 61, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 8, 16, 24, 32, 53, 54, 55, 59, 62, 63, or 64.

[0100] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 7. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 8. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:7, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:8. Further, in some such embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 1, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 2, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 3, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 4, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 5, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 6.

[0101] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 15. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 16. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 15, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 16. Further, in some such embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO:9, a HCDR2 comprising the amino acid sequence of SEQ ID NO:10, a HCDR3 comprising the amino acid sequence of SEQ ID NO:11, a LCDR1 comprising the amino acid sequence of SEQ ID NO:12, a LCDR2 comprising the amino acid sequence of SEQ ID NO:13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:14.

[0102] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 23. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:23, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:24. Further, in some such embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 18, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 19, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 22.

[0103] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 31. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 32. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:31, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:32. Further, in some such embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 25, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 27, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 28, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 30.

[0104] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 51. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 53. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:51, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:53. Further, in some such embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO:9, a HCDR2 comprising the amino acid sequence of SEQ ID NO:49, a HCDR3 comprising the amino acid sequence of SEQ ID NO:11, a LCDR1 comprising the amino acid sequence of SEQ ID NO:12, a LCDR2 comprising the amino acid sequence of SEQ ID NO:13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:14.

[0105] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 51. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 54. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:51, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:54. Further, in some such embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO:9, a HCDR2 comprising the amino acid sequence of SEQ ID NO:49, a HCDR3 comprising the amino acid sequence of SEQ ID NO:11, a LCDR1 comprising the amino acid sequence of SEQ ID NO:12, a LCDR2 comprising the amino acid sequence of SEQ ID NO:13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:14.

[0106] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 51. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 55. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:51, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:55. Further, in some such embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO:9, a HCDR2 comprising the amino acid sequence of SEQ ID NO:49, a HCDR3 comprising the amino acid sequence of SEQ ID NO:11, a LCDR1 comprising the amino acid sequence of SEQ ID NO:12, a LCDR2 comprising the amino acid sequence of SEQ ID NO:13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:14.

[0107] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 52. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 53. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:52, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:53. Further, in some such embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO:9, a HCDR2 comprising the amino acid sequence of SEQ ID NO:10, a HCDR3 comprising the amino acid sequence of SEQ ID NO:11, a LCDR1 comprising the amino acid sequence of SEQ ID NO:12, a LCDR2 comprising the amino acid sequence of SEQ ID NO:13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:14.

[0108] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 52. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 54. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:52, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:54. Further, in some such embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO:9, a HCDR2 comprising the amino acid sequence of SEQ ID NO:10, a HCDR3 comprising the amino acid sequence of SEQ ID NO:11, a LCDR1 comprising the amino acid sequence of SEQ ID NO:12, a LCDR2 comprising the amino acid sequence of SEQ ID NO:13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:14.

[0109] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 52. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 55. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:52, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:55. Further, in some such embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO:9, a HCDR2 comprising the amino acid sequence of SEQ ID NO:10, a HCDR3 comprising the amino acid sequence of SEQ ID NO:11, a LCDR1 comprising the amino acid sequence of SEQ ID NO:12, a LCDR2 comprising the amino acid sequence of SEQ ID NO:13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:14.

[0110] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 56. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 59. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:56, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:59. Further, in some such embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 18, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 19, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 22.

[0111] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 57. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 59. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:57, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:59. Further, in some such embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 18, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 19, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 22.

[0112] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 58. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 59. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:58, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:59. Further, in some such embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 18, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 19, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 22.

[0113] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 60. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 62. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:60, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:62. Further, in some such embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 25, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 27, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 28, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 30.

[0114] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 60. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 63. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:60, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:63. Further, in some such embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 25, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 27, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 28, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 30.

[0115] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 60. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 64. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:60, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:64. Further, in some such embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 25, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 27, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 28, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 30.

[0116] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 61. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 62. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:61, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:62. Further, in some such embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 25, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 27, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 28, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 30.

[0117] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 61. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 63. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:61, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:63. Further, in some such embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 25, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 27, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 28, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 30.

[0118] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 61. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 64. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:61, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:64. Further, in some such embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 25, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 27, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 28, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 30.

[0119] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:7, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:8.

[0120] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO: 15, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 16.

[0121] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO: 23, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 24.

[0122] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO: 31, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 32.

[0123] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:51, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:53.

[0124] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:51, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:54.

[0125] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:51, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:55.

[0126] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO: 52, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 53.

[0127] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO: 52, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 54.

[0128] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO: 52, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 55.

[0129] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:56, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:59.

[0130] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:57, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:59.

[0131] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:58, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:59.

[0132] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO: 60, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 62.

[0133] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO: 60, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 63.

[0134] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO: 60, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 64.

[0135] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO: 61, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 62.

[0136] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO: 61, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 63.

[0137] In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO: 61, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 64.

[0138] In the present disclosure, the antigen-binding fragment is a Fab fragment, a F(ab')2 fragment, a Fd fragment, an Fv fragment, an isolated CDR region, or a scFv. In the present disclosure, the anti-ROR1 antibody or antigen-binding fragment thereof is murine, chimeric, or humanized. Humanization can reduce immunogenicity. Therefore, in some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof is humanized.

[0139] In some embodiments, the anti-ROR1 antibodies or antigen-binding fragments thereof of the present disclosure may further comprise a constant region of an immunoglobulin, or a fragment, analog, variant or derivative of the constant region. In some embodiments, the constant region comprises a heavy chain constant region and a light chain constant region. In some embodiments, the heavy chain constant region is from a human immunoglobulin heavy chain, such as a heavy chain of IgG1, IgG2, IgG3, IgG4 or other classes of immunoglobulins. In some embodiments, the light chain constant region is from a human immunoglobulin light chain, such as a kappa light chain or a lambda light chain of a human immunoglobulin. In some embodiments, the anti-ROR1 antibody is an IgG1, IgG2, IgG3 or IgG4 isotype. In some embodiments, the constant region may comprise any modification disclosed herein or known in the art, such as insertion, deletion, substitution or chemical modification of amino acids. The C-terminal lysine (Lys 447 according to EU numbering) of the heavy chain constant region may be present or absent. In some embodiments, the constant region comprises a mutation that alters effector function. In some embodiments, any amino acid residue in the constant region can be substituted with an amino acid residue from any allotype.

[0140] In some specific embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:33, 37, 41, 45, 65, 67, 75, 77, 79, 83 or 85, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:35, 39, 43, 47, 69, 71, 73, 81, 87, 89 or 91.

[0141] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 33. In some embodiments, the anti-ROR1 antibody comprises a light chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:33, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:35. Further, in some such embodiments, the anti-ROR1 antibody further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 1, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 2, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 3, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 4, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 5, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 6.

[0142] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 37. In some embodiments, the anti-ROR1 antibody comprises a light chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 39. In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:37, and a light chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:39. Further, in some such embodiments, the anti-ROR1 antibody further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO:9, a HCDR2 comprising the amino acid sequence of SEQ ID NO:10, a HCDR3 comprising the amino acid sequence of SEQ ID NO:11, a LCDR1 comprising the amino acid sequence of SEQ ID NO:12, a LCDR2 comprising the amino acid sequence of SEQ ID NO:13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:14.

[0143] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 41. In some embodiments, the anti-ROR1 antibody comprises a light chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 43. In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:41, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:43. Further, in some such embodiments, the anti-ROR1 antibody further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 18, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 19, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 22.

[0144] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 45. In some embodiments, the anti-ROR1 antibody comprises a light chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 47. In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:45, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:47. Further, in some such embodiments, the anti-ROR1 antibody further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 25, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 27, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 28, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 30.

[0145] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 65. In some embodiments, the anti-ROR1 antibody comprises a light chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 69. In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:65, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:69. Further, in some such embodiments, the anti-ROR1 antibody further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO:9, a HCDR2 comprising the amino acid sequence of SEQ ID NO:49, a HCDR3 comprising the amino acid sequence of SEQ ID NO:11, a LCDR1 comprising the amino acid sequence of SEQ ID NO:12, a LCDR2 comprising the amino acid sequence of SEQ ID NO:13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:14.

[0146] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 65. In some embodiments, the anti-ROR1 antibody comprises a light chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 71. In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:65, and a light chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:71. Further, in some such embodiments, the anti-ROR1 antibody further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO:9, a HCDR2 comprising the amino acid sequence of SEQ ID NO:49, a HCDR3 comprising the amino acid sequence of SEQ ID NO:11, a LCDR1 comprising the amino acid sequence of SEQ ID NO:12, a LCDR2 comprising the amino acid sequence of SEQ ID NO:13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:14.

[0147] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 65. In some embodiments, the anti-ROR1 antibody comprises a light chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 73. In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:65, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:73. Further, in some such embodiments, the anti-ROR1 antibody further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO:9, a HCDR2 comprising the amino acid sequence of SEQ ID NO:49, a HCDR3 comprising the amino acid sequence of SEQ ID NO:11, a LCDR1 comprising the amino acid sequence of SEQ ID NO:12, a LCDR2 comprising the amino acid sequence of SEQ ID NO:13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:14.

[0148] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 67. In some embodiments, the anti-ROR1 antibody comprises a light chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 69. In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:67, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:69. Further, in some such embodiments, the anti-ROR1 antibody further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO:9, a HCDR2 comprising the amino acid sequence of SEQ ID NO:10, a HCDR3 comprising the amino acid sequence of SEQ ID NO:11, a LCDR1 comprising the amino acid sequence of SEQ ID NO:12, a LCDR2 comprising the amino acid sequence of SEQ ID NO:13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:14.

[0149] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 67. In some embodiments, the anti-ROR1 antibody comprises a light chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 71. In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:67, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:71. Further, in some such embodiments, the anti-ROR1 antibody further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO:9, a HCDR2 comprising the amino acid sequence of SEQ ID NO:10, a HCDR3 comprising the amino acid sequence of SEQ ID NO:11, a LCDR1 comprising the amino acid sequence of SEQ ID NO:12, a LCDR2 comprising the amino acid sequence of SEQ ID NO:13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:14.

[0150] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 67. In some embodiments, the anti-ROR1 antibody comprises a light chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 73. In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:67, and a light chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:73. Further, in some such embodiments, the anti-ROR1 antibody further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO:9, a HCDR2 comprising the amino acid sequence of SEQ ID NO:10, a HCDR3 comprising the amino acid sequence of SEQ ID NO:11, a LCDR1 comprising the amino acid sequence of SEQ ID NO:12, a LCDR2 comprising the amino acid sequence of SEQ ID NO:13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:14.

[0151] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 75. In some embodiments, the anti-ROR1 antibody comprises a light chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 81. In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:75, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:81. Further, in some such embodiments, the anti-ROR1 antibody further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 18, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 19, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 22.

[0152] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 77. In some embodiments, the anti-ROR1 antibody comprises a light chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 81. In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:77, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:81. Further, in some such embodiments, the anti-ROR1 antibody further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 18, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 19, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 22.

[0153] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 79. In some embodiments, the anti-ROR1 antibody comprises a light chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 81. In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:79, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:81. Further, in some such embodiments, the anti-ROR1 antibody further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 18, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 19, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 22.

[0154] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 83. In some embodiments, the anti-ROR1 antibody comprises a light chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 87. In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:83, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:87. Further, in some such embodiments, the anti-ROR1 antibody further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 25, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 27, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 28, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 30.

[0155] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 83. In some embodiments, the anti-ROR1 antibody comprises a light chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 89. In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:83, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:89. Further, in some such embodiments, the anti-ROR1 antibody further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 25, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 27, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 28, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 30.

[0156] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 83. In some embodiments, the anti-ROR1 antibody comprises a light chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 91. In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:83, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:91. Further, in some such embodiments, the anti-ROR1 antibody further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 25, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 27, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 28, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 30.

[0157] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 85. In some embodiments, the anti-ROR1 antibody comprises a light chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 87. In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:85, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:87. Further, in some such embodiments, the anti-ROR1 antibody further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 25, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 27, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 28, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 30.

[0158] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 85. In some embodiments, the anti-ROR1 antibody comprises a light chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 89. In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:85, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:89. Further, in some such embodiments, the anti-ROR1 antibody further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 25, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 27, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 28, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 30.

[0159] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 85. In some embodiments, the anti-ROR1 antibody comprises a light chain having an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 91. In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:85, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:91. Further, in some such embodiments, the anti-ROR1 antibody further comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 25, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 27, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 28, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 30.

[0160] In some embodiments, the anti-ROR1 antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:33, and a light chain comprising the amino acid sequence shown in SEQ ID NO:35.

[0161] In some embodiments, the anti-ROR1 antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:37, and a light chain comprising the amino acid sequence shown in SEQ ID NO:39.

[0162] In some embodiments, the anti-ROR1 antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:41, and a light chain comprising the amino acid sequence shown in SEQ ID NO:43.

[0163] In some embodiments, the anti-ROR1 antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:45, and a light chain comprising the amino acid sequence shown in SEQ ID NO:47.

[0164] In some embodiments, the anti-ROR1 antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:65, and a light chain comprising the amino acid sequence shown in SEQ ID NO:69.

[0165] In some embodiments, the anti-ROR1 antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:65, and a light chain comprising the amino acid sequence shown in SEQ ID NO:71.

[0166] In some embodiments, the anti-ROR1 antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:65, and a light chain comprising the amino acid sequence shown in SEQ ID NO:73.

[0167] In some embodiments, the anti-ROR1 antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:67, and a light chain comprising the amino acid sequence shown in SEQ ID NO:69.

[0168] In some embodiments, the anti-ROR1 antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:67, and a light chain comprising the amino acid sequence shown in SEQ ID NO:71.

[0169] In some embodiments, the anti-ROR1 antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:67, and a light chain comprising the amino acid sequence shown in SEQ ID NO:73.

[0170] In some embodiments, the anti-ROR1 antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:75, and a light chain comprising the amino acid sequence shown in SEQ ID NO:81.

[0171] In some embodiments, the anti-ROR1 antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:77, and a light chain comprising the amino acid sequence shown in SEQ ID NO:81.

[0172] In some embodiments, the anti-ROR1 antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:79, and a light chain comprising the amino acid sequence shown in SEQ ID NO:81.

[0173] In some embodiments, the anti-ROR1 antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:83, and a light chain comprising the amino acid sequence shown in SEQ ID NO:87.

[0174] In some embodiments, the anti-ROR1 antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:83, and a light chain comprising the amino acid sequence shown in SEQ ID NO:89.

[0175] In some embodiments, the anti-ROR1 antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:83, and a light chain comprising the amino acid sequence shown in SEQ ID NO:91.

[0176] In some embodiments, the anti-ROR1 antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:85, and a light chain comprising the amino acid sequence shown in SEQ ID NO:87.

[0177] In some embodiments, the anti-ROR1 antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:85, and a light chain comprising the amino acid sequence shown in SEQ ID NO:89.

[0178] In some embodiments, the anti-ROR1 antibody comprises: a heavy chain comprising the amino acid sequence shown in SEQ ID NO:85, and a light chain comprising the amino acid sequence shown in SEQ ID NO:91.

[0179] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO:33, and a light chain having an amino acid sequence as shown in SEQ ID NO:35.

[0180] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO:37, and a light chain having an amino acid sequence as shown in SEQ ID NO:39.

[0181] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO:41, and a light chain having an amino acid sequence as shown in SEQ ID NO:43.

[0182] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO:45, and a light chain having an amino acid sequence as shown in SEQ ID NO:47.

[0183] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO:65, and a light chain having an amino acid sequence as shown in SEQ ID NO:69.

[0184] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO:65, and a light chain having an amino acid sequence as shown in SEQ ID NO:71.

[0185] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO:65, and a light chain having an amino acid sequence as shown in SEQ ID NO:73.

[0186] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO:67, and a light chain having an amino acid sequence as shown in SEQ ID NO:69.

[0187] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO:67, and a light chain having an amino acid sequence as shown in SEQ ID NO:71.

[0188] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO: 67, and a light chain having an amino acid sequence as shown in SEQ ID NO: 73.

[0189] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO:75, and a light chain having an amino acid sequence as shown in SEQ ID NO:81.

[0190] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO:77, and a light chain having an amino acid sequence as shown in SEQ ID NO:81.

[0191] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO:79, and a light chain having an amino acid sequence as shown in SEQ ID NO:81.

[0192] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO:83, and a light chain having an amino acid sequence as shown in SEQ ID NO:87.

[0193] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO:83, and a light chain having an amino acid sequence as shown in SEQ ID NO:89.

[0194] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO:83, and a light chain having an amino acid sequence as shown in SEQ ID NO:91.

[0195] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO:85, and a light chain having an amino acid sequence as shown in SEQ ID NO:87.

[0196] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO:85, and a light chain having an amino acid sequence as shown in SEQ ID NO:89.

[0197] In some embodiments, the anti-ROR1 antibody comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO:85, and a light chain having an amino acid sequence as shown in SEQ ID NO:91.

[0198] In some embodiments, the amino acid sequence of the heavy chain of the anti-ROR1 antibody is shown in SEQ ID NO:33, and the amino acid sequence of the light chain is shown in SEQ ID NO:35.

[0199] In some embodiments, the amino acid sequence of the heavy chain of the anti-ROR1 antibody is shown in SEQ ID NO:37, and the amino acid sequence of the light chain is shown in SEQ ID NO:39.

[0200] In some embodiments, the amino acid sequence of the heavy chain of the anti-ROR1 antibody is shown in SEQ ID NO:41, and the amino acid sequence of the light chain is shown in SEQ ID NO:43.

[0201] In some embodiments, the amino acid sequence of the heavy chain of the anti-ROR1 antibody is shown in SEQ ID NO:45, and the amino acid sequence of the light chain is shown in SEQ ID NO:47.

[0202] In some embodiments, the amino acid sequence of the heavy chain of the anti-ROR1 antibody is shown in SEQ ID NO:65, and the amino acid sequence of the light chain is shown in SEQ ID NO:69.

[0203] In some embodiments, the amino acid sequence of the heavy chain of the anti-ROR1 antibody is shown in SEQ ID NO:65, and the amino acid sequence of the light chain is shown in SEQ ID NO:71.

[0204] In some embodiments, the amino acid sequence of the heavy chain of the anti-ROR1 antibody is shown in SEQ ID NO:65, and the amino acid sequence of the light chain is shown in SEQ ID NO:73.

[0205] In some embodiments, the amino acid sequence of the heavy chain of the anti-ROR1 antibody is shown in SEQ ID NO:67, and the amino acid sequence of the light chain is shown in SEQ ID NO:69.

[0206] In some embodiments, the amino acid sequence of the heavy chain of the anti-ROR1 antibody is shown in SEQ ID NO:67, and the amino acid sequence of the light chain is shown in SEQ ID NO:71.

[0207] In some embodiments, the amino acid sequence of the heavy chain of the anti-ROR1 antibody is shown in SEQ ID NO:67, and the amino acid sequence of the light chain is shown in SEQ ID NO:73.

[0208] In some embodiments, the amino acid sequence of the heavy chain of the anti-ROR1 antibody is shown in SEQ ID NO:75, and the amino acid sequence of the light chain is shown in SEQ ID NO:81.

[0209] In some embodiments, the amino acid sequence of the heavy chain of the anti-ROR1 antibody is shown in SEQ ID NO:77, and the amino acid sequence of the light chain is shown in SEQ ID NO:81.

[0210] In some embodiments, the amino acid sequence of the heavy chain of the anti-ROR1 antibody is shown in SEQ ID NO:79, and the amino acid sequence of the light chain is shown in SEQ ID NO:81.

[0211] In some embodiments, the amino acid sequence of the heavy chain of the anti-ROR1 antibody is shown in SEQ ID NO:83, and the amino acid sequence of the light chain is shown in SEQ ID NO:87.

[0212] In some embodiments, the amino acid sequence of the heavy chain of the anti-ROR1 antibody is shown in SEQ ID NO:83, and the amino acid sequence of the light chain is shown in SEQ ID NO:89.

[0213] In some embodiments, the amino acid sequence of the heavy chain of the anti-ROR1 antibody is shown in SEQ ID NO:83, and the amino acid sequence of the light chain is shown in SEQ ID NO:91.

[0214] In some embodiments, the amino acid sequence of the heavy chain of the anti-ROR1 antibody is shown in SEQ ID NO:85, and the amino acid sequence of the light chain is shown in SEQ ID NO:87.

[0215] In some embodiments, the amino acid sequence of the heavy chain of the anti-ROR1 antibody is shown in SEQ ID NO:85, and the amino acid sequence of the light chain is shown in SEQ ID NO:89.

[0216] In some embodiments, the amino acid sequence of the heavy chain of the anti-ROR1 antibody is shown in SEQ ID NO:85, and the amino acid sequence of the light chain is shown in SEQ ID NO:91.

[0217] It should be understood that the anti-ROR1 antibodies referred to herein also include anti-ROR1 antibodies with a heavy chain C-terminal lysine (Lys 447 according to EU numbering) deleted.

[0218] Tables S1 and S2 provide some exemplary anti-ROR1 antibodies or antigen-binding fragments thereof (e.g., chimeric antibodies ch3G9B1, ch29H5D8, ch135A2B10, ch137G11D10 and humanized antibodies hz29H5D8-1.1, hz29H5D8-1.2, hz29H5D8-2.1, hz29H5D8-2.2, hz29H5D8-3.1, hz29H5D8-3. 2. Amino acid sequence information of the CDRs and variable regions of hz135A2B10-1.1, hz135A2B10-1.2, hz135A2B10-1.3, hz137G11D10-1.1, hz137G11D10-1.2, hz137G11D10-2.1, hz137G11D10-2.2, hz137G11D10-3.1, hz137G11D10-3.2).

[0219] Table S1. Amino acid sequences of CDRs and variable regions (SEQ ID NO:

[0220] Any of the anti-ROR1 antibodies or antigen-binding fragments thereof provided herein has good antigen-binding activity. Any of the anti-ROR1 antibodies or antigen-binding fragments thereof disclosed herein can bind to human ROR1 and / or monkey ROR1. In some embodiments, any of the anti-ROR1 antibodies or antigen-binding fragments thereof disclosed herein can be measured by surface plasmon resonance (SPR) to measure the following K DBinds to human ROR1: 5E-08M or less, 2.71E-08M or less, 2E-08M or less, 1E-08M or less, 5E-09M or less, 2E-09M or less, 1.17E-09M or less, 1E-09M or less, 6.69E-10M or less, 6.1E-10M or less, 5.89E-10M or less, 5.86E-10M or less, 5.75 In some embodiments, any of the anti-ROR1 antibodies or antigen-binding fragments thereof of the present disclosure may have a K of 0.05E-10 or less, as measured by surface plasmon resonance (SPR) technology. D Binds to monkey ROR1: 5E-08M or less, 2.71E-08M or less, 2E-08M or less, 1E-08M or less, 5E-09M or less, 2E-09M or less, 1.17E-09M or less, 1E-09M or less, 6.69E-10M or less, 6.1E-10M or less, 5.89E-10M or less, 5.86E-10M or less, 5.75 E-10M or less, 5.69E-10M or less, 5.27E-10M or less, 5E-10M or less, 3.43E-10M or less, 2.89E-10M or less, 1.97E-10M or less, 1.72E-10M or less, 1.6E-10M or less, 1.45E-10M or less, 1.12E-10M or less, or 1.05E-10M or less.

[0221] Any of the anti-ROR1 antibodies or antigen-binding fragments thereof provided by the present disclosure can be effectively internalized in cells expressing ROR1.

[0222] Any of the anti-ROR1 antibodies or antigen-binding fragments thereof provided herein can inhibit the non-canonical Wnt signaling pathway stimulated by Wnt5a in cells expressing ROR1. In some embodiments, the anti-ROR1 antibody or antigen-binding fragment thereof can inhibit the non-canonical Wnt signaling pathway stimulated by Wnt5a at 20 nM or less, 10 nM or less, 5 nM or less, or 2.5 nM or less. In some embodiments, any of the anti-ROR1 antibodies or antigen-binding fragments thereof disclosed herein has an inhibition rate of 10% or more, 15% or more, or 20% or more on the non-canonical Wnt signaling pathway stimulated by Wnt5a at a concentration of 20 nM.

[0223] Any of the anti-ROR1 antibodies or antigen-binding fragments thereof provided by the present disclosure can exert ADCC effects on cells expressing ROR1.

[0224] Any of the anti-ROR1 antibodies or antigen-binding fragments thereof provided herein can induce tumor growth regression in vivo. In some embodiments, the tumor is a tumor that expresses ROR1.

[0225] Any of the anti-ROR1 antibodies or antigen-binding fragments thereof provided herein can delay tumor growth in vivo. In some embodiments, the tumor is a tumor that expresses ROR1.

[0226] Any of the anti-ROR1 antibodies or antigen-binding fragments thereof disclosed herein has a good safety profile.

[0227] In some embodiments, the anti-ROR1 antibody or its antigen-binding fragment is a monoclonal antibody. In some embodiments, the anti-ROR1 antibody or its antigen-binding fragment is a monospecific antibody. In some embodiments, the anti-ROR1 antibody or its antigen-binding fragment is a multispecific antibody (e.g., a bispecific antibody, a trispecific antibody, etc.).

[0228] Isolated nucleic acids

[0229] The present disclosure provides an isolated nucleic acid comprising a nucleotide sequence encoding the anti-ROR1 antibody or antigen-binding fragment thereof of the present disclosure. Some nucleotide sequences encoding the anti-ROR1 antibody or antigen-binding fragment thereof are exemplified in the sequence listing.

[0230] carrier

[0231] The present disclosure provides vectors comprising the nucleic acid. In some embodiments, the vector is a cloning vector. In other embodiments, the vector is an expression vector. In a specific example, the expression vector is pcDNA3.1(+). The expression vector can optionally be any expression vector capable of expressing the anti-ROR1 antibody or antigen-binding fragment thereof described herein.

[0232] host cells

[0233] The present disclosure provides host cells comprising nucleic acids of the present disclosure or vectors of the present disclosure. In some embodiments, the host cell is a suitable host cell for cloning or expressing an anti-ROR1 antibody or an antigen-binding fragment thereof. In some embodiments, the host cell is a prokaryotic cell. In other embodiments, the host cell is a eukaryotic cell. In some embodiments, the host cell is selected from yeast cells, mammalian cells, or other cells suitable for preparing anti-ROR1 antibodies or antigen-binding fragments thereof. Mammalian cells are, for example, Chinese hamster ovary (CHO) cells or CHO-S cells.

[0234] Fusion protein

[0235] In some embodiments, the present disclosure provides fusion proteins comprising an anti-ROR1 antibody or antigen-binding fragment thereof of the present disclosure.

[0236] Antibody-drug conjugates (ADCs)

[0237] The present disclosure provides an antibody-drug conjugate comprising the anti-ROR1 antibody or antigen-binding fragment thereof of the present disclosure. In some embodiments, the antibody-drug conjugate comprises the anti-ROR1 antibody or antigen-binding fragment thereof and a cytotoxic drug.

[0238] Chimeric Antigen Receptor (CAR)

[0239] The present disclosure also provides an anti-ROR1 chimeric antigen receptor (CAR) comprising the anti-ROR1 antibody or antigen-binding fragment thereof of the present disclosure.

[0240] The anti-ROR1 CAR may comprise (a) an extracellular antigen binding domain that binds to ROR1; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0241] The present disclosure also provides engineered immune effector cells comprising the CAR of the present disclosure. In some embodiments, the immune effector cells are T cells, NK cells, peripheral blood mononuclear cells (PBMC), hematopoietic stem cells, pluripotent stem cells or embryonic stem cells.

[0242] Pharmaceutical composition

[0243] The present disclosure provides pharmaceutical compositions comprising an anti-ROR1 antibody or antigen-binding fragment thereof, fusion protein, antibody-drug conjugate, or engineered immune effector cell of the present disclosure, and further comprising one or more pharmaceutically acceptable excipients. Pharmaceutically acceptable excipients include, for example, excipients, diluents, encapsulating materials, fillers, buffers, or other agents.

[0244] Method for preparing anti-ROR1 antibody or antigen-binding fragment thereof

[0245] In some embodiments, the present disclosure provides a method for preparing an anti-ROR1 antibody or an antigen-binding fragment thereof, the method comprising: culturing the host cell to express the anti-ROR1 antibody or its antigen-binding fragment, and isolating and purifying the anti-ROR1 antibody or its antigen-binding fragment in the system. In order to produce the anti-ROR1 antibody or its antigen-binding fragment, the nucleic acid encoding the anti-ROR1 antibody or its antigen-binding fragment is isolated and inserted into one or more vectors for further cloning and / or expression in the host cell. The nucleic acid can be obtained by various methods well known in the art, such as gene splicing and chemical synthesis.

[0246] The purity of the anti-ROR1 antibody or antigen-binding fragment thereof can be determined by any of a variety of well-known analytical methods, such as gel electrophoresis, high performance liquid chromatography, size exclusion chromatography, and the like.

[0247] The physicochemical properties and / or biological activities of the anti-ROR1 antibodies or antigen-binding fragments thereof of the present disclosure can be identified, screened, or characterized by various assays known in the art.

[0248] use

[0249] The present disclosure provides uses of the anti-ROR1 antibodies or antigen-binding fragments thereof. In some specific embodiments, the anti-ROR1 antibodies used may be ch3G9B1, ch29H5D8, ch135A2B10, ch137G11D10, hz29H5D8-1.1, hz29H5D8-1.2, hz29H5D8-2.1, hz29H5D8-2.2, hz29H5D8-3.1, hz29H5D8-3.2, hz135A2B10-1.1, hz135A2B10-1.2, hz135A2B10-1.3, hz137G11D10-1.1, hz137G11D10-1.2, hz137G11D10-2.1, hz137G11D10-2.2, hz137G11D10-3.1 or / and hz137G11D10-3.2.

[0250] The present disclosure provides use of the anti-ROR1 antibody or antigen-binding fragment thereof, the fusion protein, the antibody-drug conjugate, the engineered immune effector cell, or the pharmaceutical composition in preparing a medicament for treating a disease expressing ROR1.

[0251] The present disclosure provides a method for treating a disease that expresses ROR1, comprising administering the anti-ROR1 antibody or its antigen-binding fragment, the fusion protein, the antibody-drug conjugate, the engineered immune effector cell, or the pharmaceutical composition to a subject in need thereof. The present disclosure provides a method for treating a disease that expresses ROR1, comprising administering a therapeutically effective amount of the anti-ROR1 antibody or its antigen-binding fragment, the fusion protein, the antibody-drug conjugate, the engineered immune effector cell, or the pharmaceutical composition to a subject in need thereof. In some embodiments, the disease is a tumor.

[0252] In some embodiments, the method comprises contacting tumor cells with the anti-ROR1 antibody or antigen-binding fragment thereof, the fusion protein, the antibody-drug conjugate, the engineered immune effector cell, or the pharmaceutical composition, thereby killing the tumor cells or inhibiting tumor cell growth.

[0253] In some embodiments, the tumor is a non-solid tumor. In some embodiments, the tumor is a hematological tumor. In some embodiments, the tumor is a solid tumor. In some embodiments, the tumor is a leukemia, lymphoma, multiple myeloma, breast cancer, ovarian cancer, ovarian teratoma, colon cancer, lung cancer (including small cell lung cancer and non-small cell lung cancer), skin cancer, pancreatic cancer, testicular cancer, bladder cancer, uterine cancer, prostate cancer, or adrenal cancer. In some embodiments, the lymphoma is mantle cell lymphoma (MCL).

[0254] Reagent test kit

[0255] The present disclosure provides a kit comprising an anti-ROR1 antibody or its antigen-binding fragment, fusion protein, antibody-drug conjugate, engineered immune effector cell or pharmaceutical composition of the present disclosure. In some embodiments, the kit can be used to implement the use or other uses of the anti-ROR1 antibody or its antigen-binding fragment, fusion protein, antibody-drug conjugate, engineered immune effector cell or pharmaceutical composition provided by the present disclosure. In some embodiments, the kit may include an anti-ROR1 antibody or its antigen-binding fragment, fusion protein, antibody-drug conjugate, engineered immune effector cell or pharmaceutical composition of the present disclosure, and a reagent for detecting the presence of ROR1 in a biological sample. The kit may also include instructions for use. The kit may also include other materials required from a commercial and user perspective, for example, other buffers, diluents, needles, syringes, etc. DETAILED DESCRIPTION

[0256] The present disclosure also provides the following specific implementation schemes, but the protection scope of the present disclosure is not limited thereto:

[0257] Embodiment 1. An anti-ROR1 antibody or an antigen-binding fragment thereof, comprising: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 1, 9, 17 or 25, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 2, 10, 18, 26, 49 or 50, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 3, 11, 19 or 27, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 4, 12, 20 or 28, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 5, 13, 21 or 29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 6, 14, 22 or 30.

[0258] Embodiment 2. The anti-ROR1 antibody or antigen-binding fragment thereof according to embodiment 1, wherein the anti-ROR1 antibody or antigen-binding fragment thereof comprises:

[0259] (1) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 1, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 2, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 3, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 4, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 5, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 6;

[0260] (2) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 9, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 50, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 11, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 14;

[0261] (3) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 9, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 10, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 11, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 14;

[0262] (4) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 9, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 49, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 11, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 14;

[0263] (5) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 18, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 19, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 22; or

[0264] (6) HCDR1 comprising the amino acid sequence of SEQ ID NO: 25, HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, HCDR3 comprising the amino acid sequence of SEQ ID NO: 27, LCDR1 comprising the amino acid sequence of SEQ ID NO: 28, LCDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 30.

[0265] Embodiment 3. An anti-ROR1 antibody or an antigen-binding fragment thereof, comprising: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in the amino acid sequence of SEQ ID NO: 7, 15, 23, 31, 51, 52, 56, 57, 58, 60 or 61, and LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in the amino acid sequence of SEQ ID NO: 8, 16, 24, 32, 53, 54, 55, 59, 62, 63 or 64.

[0266] Embodiment 4. The anti-ROR1 antibody or antigen-binding fragment thereof according to embodiment 3, wherein the anti-ROR1 antibody or antigen-binding fragment thereof comprises:

[0267] (1) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region as shown in SEQ ID NO: 7, and LCDR1, LCDR2, and LCDR3 in the light chain variable region as shown in SEQ ID NO: 8;

[0268] (2) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region as shown in SEQ ID NO: 15, and LCDR1, LCDR2, and LCDR3 in the light chain variable region as shown in SEQ ID NO: 16;

[0269] (3) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region as shown in SEQ ID NO: 23, and LCDR1, LCDR2, and LCDR3 in the light chain variable region as shown in SEQ ID NO: 24;

[0270] (4) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region as shown in SEQ ID NO: 31, and LCDR1, LCDR2, and LCDR3 in the light chain variable region as shown in SEQ ID NO: 32;

[0271] (5) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region as shown in SEQ ID NO: 51, and LCDR1, LCDR2, and LCDR3 in the light chain variable region as shown in SEQ ID NO: 53;

[0272] (6) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region as shown in SEQ ID NO: 51, and LCDR1, LCDR2, and LCDR3 in the light chain variable region as shown in SEQ ID NO: 54;

[0273] (7) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region as shown in SEQ ID NO: 51, and LCDR1, LCDR2, and LCDR3 in the light chain variable region as shown in SEQ ID NO: 55;

[0274] (8) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region as shown in SEQ ID NO: 52, and LCDR1, LCDR2, and LCDR3 in the light chain variable region as shown in SEQ ID NO: 53;

[0275] (9) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having an amino acid sequence as shown in SEQ ID NO: 52, and LCDR1, LCDR2, and LCDR3 in the light chain variable region having an amino acid sequence as shown in SEQ ID NO: 54;

[0276] (10) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region represented by the amino acid sequence of SEQ ID NO: 52, and LCDR1, LCDR2, and LCDR3 in the light chain variable region represented by the amino acid sequence of SEQ ID NO: 55;

[0277] (11) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region represented by the amino acid sequence of SEQ ID NO: 56, and LCDR1, LCDR2, and LCDR3 in the light chain variable region represented by the amino acid sequence of SEQ ID NO: 59;

[0278] (12) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region represented by the amino acid sequence of SEQ ID NO: 57, and LCDR1, LCDR2, and LCDR3 in the light chain variable region represented by the amino acid sequence of SEQ ID NO: 59;

[0279] (13) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region represented by the amino acid sequence of SEQ ID NO: 58, and LCDR1, LCDR2, and LCDR3 in the light chain variable region represented by the amino acid sequence of SEQ ID NO: 59;

[0280] (14) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having an amino acid sequence as shown in SEQ ID NO: 60, and LCDR1, LCDR2, and LCDR3 in the light chain variable region having an amino acid sequence as shown in SEQ ID NO: 62;

[0281] (15) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region represented by the amino acid sequence of SEQ ID NO: 60, and LCDR1, LCDR2, and LCDR3 in the light chain variable region represented by the amino acid sequence of SEQ ID NO: 63;

[0282] (16) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region whose amino acid sequences are as shown in SEQ ID NO: 60, and LCDR1, LCDR2, and LCDR3 in the light chain variable region whose amino acid sequences are as shown in SEQ ID NO: 64;

[0283] (17) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region whose amino acid sequences are as shown in SEQ ID NO: 61, and LCDR1, LCDR2, and LCDR3 in the light chain variable region whose amino acid sequences are as shown in SEQ ID NO: 62;

[0284] (18) HCDR1, HCDR2, and HCDR3 in the heavy chain variable region of the amino acid sequence shown in SEQ ID NO: 61, and LCDR1, LCDR2, and LCDR3 in the light chain variable region of the amino acid sequence shown in SEQ ID NO: 63; or

[0285] (19) HCDR1, HCDR2 and HCDR3 in the heavy chain variable region whose amino acid sequences are as shown in SEQ ID NO: 61, and LCDR1, LCDR2 and LCDR3 in the light chain variable region whose amino acid sequences are as shown in SEQ ID NO: 64.

[0286] Embodiment 5. An anti-ROR1 antibody or antigen-binding fragment thereof according to any one of Embodiments 1-4, wherein the anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region whose amino acid sequence is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO: 7, 15, 23, 31, 51, 52, 56, 57, 58, 60 or 61.

[0287] Embodiment 6. An anti-ROR1 antibody or antigen-binding fragment thereof according to any one of Embodiments 1-5, wherein the anti-ROR1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO: 8, 16, 24, 32, 53, 54, 55, 59, 62, 63 or 64.

[0288] Embodiment 7. The anti-ROR1 antibody or antigen-binding fragment thereof according to any one of Embodiments 1-6, wherein the anti-ROR1 antibody or antigen-binding fragment thereof comprises:

[0289] (1) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:7, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:8;

[0290] (2) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 15, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 16;

[0291] (3) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:23, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:24;

[0292] (4) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:31, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:32;

[0293] (5) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:51, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:53;

[0294] (6) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:51, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:54;

[0295] (7) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:51, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:55;

[0296] (8) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:52, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:53;

[0297] (9) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:52, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:54;

[0298] (10) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:52, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:55;

[0299] (11) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:56, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:59;

[0300] (12) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:57, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:59;

[0301] (13) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:58, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:59;

[0302] (14) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:60, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:62;

[0303] (15) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:60, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:63;

[0304] (16) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:60, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:64;

[0305] (17) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:61, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:62;

[0306] (18) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:61, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:63; or

[0307] (19) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:61, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:64.

[0308] Embodiment 8. The anti-ROR1 antibody or antigen-binding fragment thereof according to any one of Embodiments 1-7, wherein the anti-ROR1 antibody or antigen-binding fragment thereof comprises:

[0309] (1) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8;

[0310] (2) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 15, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 16;

[0311] (3) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 23, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 24;

[0312] (4) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 31, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 32;

[0313] (5) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 51, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 53;

[0314] (6) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 51, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 54;

[0315] (7) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 51, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 55;

[0316] (8) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 52, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 53;

[0317] (9) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 52, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 54;

[0318] (10) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 52, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 55;

[0319] (11) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 56, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 59;

[0320] (12) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 57, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 59;

[0321] (13) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 58, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 59;

[0322] (14) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 60, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 62;

[0323] (15) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 60, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 63;

[0324] (16) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 60, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 64;

[0325] (17) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 61, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 62;

[0326] (18) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 61, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 63; or

[0327] (19) A heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO: 61, and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 64.

[0328] Embodiment 9. The anti-ROR1 antibody or antigen-binding fragment thereof according to any one of Embodiments 1-8, wherein the antigen-binding fragment is a Fab fragment, a F(ab')2 fragment, a Fd fragment, an Fv fragment, an isolated CDR region, or a scFv.

[0329] Embodiment 10. The anti-ROR1 antibody or antigen-binding fragment thereof according to any one of Embodiments 1-9, wherein the anti-ROR1 antibody or antigen-binding fragment thereof is murine, chimeric or humanized.

[0330] Embodiment 11. The anti-ROR1 antibody or antigen-binding fragment thereof according to any one of Embodiments 1-10, wherein the anti-ROR1 antibody is of IgG1, IgG2, IgG3 or IgG4 isotype.

[0331] Embodiment 12. An anti-ROR1 antibody or antigen-binding fragment thereof according to any one of Embodiments 1-11, wherein the anti-ROR1 antibody comprises a heavy chain whose amino acid sequence is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO: 33, 37, 41, 45, 65, 67, 75, 77, 79, 83 or 85.

[0332] Embodiment 13. An anti-ROR1 antibody or antigen-binding fragment thereof according to any one of Embodiments 1-12, wherein the anti-ROR1 antibody comprises a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO: 35, 39, 43, 47, 69, 71, 73, 81, 87, 89 or 91.

[0333] Embodiment 14. The anti-ROR1 antibody or antigen-binding fragment thereof according to any one of Embodiments 1-13, wherein the anti-ROR1 antibody comprises:

[0334] (1) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:33, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:35;

[0335] (2) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:37, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:39;

[0336] (3) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:41, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:43;

[0337] (4) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:45, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:47;

[0338] (5) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:65, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:69;

[0339] (6) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:65, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:71;

[0340] (7) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:65, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:73;

[0341] (8) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:67, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:69;

[0342] (9) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:67, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:71;

[0343] (10) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:67, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:73;

[0344] (11) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:75, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:81;

[0345] (12) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:77, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:81;

[0346] (13) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:79, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:81;

[0347] (14) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:83, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:87;

[0348] (15) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:83, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:89;

[0349] (16) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:83, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:91;

[0350] (17) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:85, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:87;

[0351] (18) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:85, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:89; or

[0352] (19) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:85, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:91.

[0353] Embodiment 15. The anti-ROR1 antibody or antigen-binding fragment thereof according to any one of Embodiments 1-14, wherein the anti-ROR1 antibody comprises:

[0354] (1) a heavy chain comprising the amino acid sequence of SEQ ID NO: 33, and a light chain comprising the amino acid sequence of SEQ ID NO: 35;

[0355] (2) a heavy chain comprising the amino acid sequence of SEQ ID NO: 37, and a light chain comprising the amino acid sequence of SEQ ID NO: 39;

[0356] (3) a heavy chain comprising the amino acid sequence of SEQ ID NO:41, and a light chain comprising the amino acid sequence of SEQ ID NO:43;

[0357] (4) a heavy chain comprising the amino acid sequence of SEQ ID NO:45, and a light chain comprising the amino acid sequence of SEQ ID NO:47;

[0358] (5) a heavy chain comprising the amino acid sequence of SEQ ID NO: 65, and a light chain comprising the amino acid sequence of SEQ ID NO: 69;

[0359] (6) a heavy chain comprising the amino acid sequence of SEQ ID NO: 65, and a light chain comprising the amino acid sequence of SEQ ID NO: 71;

[0360] (7) a heavy chain comprising the amino acid sequence of SEQ ID NO: 65, and a light chain comprising the amino acid sequence of SEQ ID NO: 73;

[0361] (8) a heavy chain comprising the amino acid sequence of SEQ ID NO: 67, and a light chain comprising the amino acid sequence of SEQ ID NO: 69;

[0362] (9) a heavy chain comprising the amino acid sequence of SEQ ID NO: 67, and a light chain comprising the amino acid sequence of SEQ ID NO: 71;

[0363] (10) a heavy chain comprising the amino acid sequence of SEQ ID NO: 67, and a light chain comprising the amino acid sequence of SEQ ID NO: 73;

[0364] (11) a heavy chain comprising the amino acid sequence of SEQ ID NO: 75, and a light chain comprising the amino acid sequence of SEQ ID NO: 81;

[0365] (12) a heavy chain comprising the amino acid sequence of SEQ ID NO: 77, and a light chain comprising the amino acid sequence of SEQ ID NO: 81;

[0366] (13) a heavy chain comprising the amino acid sequence of SEQ ID NO: 79, and a light chain comprising the amino acid sequence of SEQ ID NO: 81;

[0367] (14) a heavy chain comprising the amino acid sequence of SEQ ID NO: 83, and a light chain comprising the amino acid sequence of SEQ ID NO: 87;

[0368] (15) a heavy chain comprising the amino acid sequence of SEQ ID NO: 83, and a light chain comprising the amino acid sequence of SEQ ID NO: 89;

[0369] (16) a heavy chain comprising the amino acid sequence of SEQ ID NO: 83, and a light chain comprising the amino acid sequence of SEQ ID NO: 91;

[0370] (17) a heavy chain comprising the amino acid sequence of SEQ ID NO: 85, and a light chain comprising the amino acid sequence of SEQ ID NO: 87;

[0371] (18) a heavy chain comprising the amino acid sequence of SEQ ID NO: 85, and a light chain comprising the amino acid sequence of SEQ ID NO: 89; or

[0372] (19) A heavy chain comprising the amino acid sequence shown in SEQ ID NO: 85, and a light chain comprising the amino acid sequence shown in SEQ ID NO: 91.

[0373] Embodiment 16. The anti-ROR1 antibody or antigen-binding fragment thereof according to any one of embodiments 1-15, wherein the anti-ROR1 antibody or antigen-binding fragment thereof has one or more of the following properties:

[0374] (1) Binding to human ROR1; preferably, measured by surface plasmon resonance, with K D binds human ROR1 at 5E-08 M or less, 1E-09 M or less, or 5E-10 M or less;

[0375] (2) Binding to monkey ROR1; preferably, measured by surface plasmon resonance, with K D binds human ROR1 at 5E-08 M or less, 1E-09 M or less, or 5E-10 M or less;

[0376] (3) inhibiting the non-canonical Wnt signaling pathway stimulated by Wnt5a; preferably, the anti-ROR1 antibody or antigen-binding fragment thereof has an inhibition rate of 10% or more, 15% or more, or 20% or more on the non-canonical Wnt signaling pathway stimulated by Wnt5a at a concentration of 20 nM;

[0377] (4) plays an internalization role in cells expressing ROR1;

[0378] (5) exert ADCC effect on cells expressing ROR1;

[0379] (6) inducing regression of tumor growth in vivo; and

[0380] (7) Delaying tumor growth in vivo.

[0381] Embodiment 17. The anti-ROR1 antibody or antigen-binding fragment thereof according to any one of Embodiments 1-16, wherein the anti-ROR1 antibody or antigen-binding fragment thereof is a monospecific antibody or a multispecific antibody.

[0382] Embodiment 18. An isolated nucleic acid comprising a nucleotide sequence encoding the anti-ROR1 antibody or antigen-binding fragment thereof according to any one of embodiments 1-17.

[0383] Embodiment 19. A vector comprising the nucleic acid of embodiment 18.

[0384] Embodiment 20. A host cell comprising the nucleic acid of embodiment 18, or the vector of embodiment 19.

[0385] Embodiment 21. A method for preparing the anti-ROR1 antibody or antigen-binding fragment thereof according to any one of Embodiments 1-17, comprising culturing the host cell according to Embodiment 20 to express the anti-ROR1 antibody or antigen-binding fragment thereof, and isolating and purifying the anti-ROR1 antibody or antigen-binding fragment thereof in the system.

[0386] Embodiment 22. A fusion protein comprising the anti-ROR1 antibody or antigen-binding fragment thereof according to any one of embodiments 1-17.

[0387] Embodiment 23. An antibody-drug conjugate comprising the anti-ROR1 antibody or antigen-binding fragment thereof according to any one of embodiments 1-17.

[0388] Embodiment 24. A chimeric antigen receptor comprising the anti-ROR1 antibody or antigen-binding fragment thereof according to any one of embodiments 1-17.

[0389] Embodiment 25. An engineered immune effector cell comprising the chimeric antigen receptor of embodiment 24.

[0390] Embodiment 26. A pharmaceutical composition comprising the anti-ROR1 antibody or antigen-binding fragment thereof according to any one of embodiments 1-17, the fusion protein of embodiment 22, the antibody-drug conjugate of embodiment 23, or the engineered immune effector cell of embodiment 25, and one or more pharmaceutically acceptable excipients.

[0391] Embodiment 27. Use of the anti-ROR1 antibody or antigen-binding fragment thereof according to any one of Embodiments 1-17, the fusion protein according to Embodiment 22, the antibody-drug conjugate according to Embodiment 23, the engineered immune effector cell according to Embodiment 25, or the pharmaceutical composition according to Embodiment 26 in the preparation of a medicament for treating a disease expressing ROR1.

[0392] Embodiment 28. The use according to embodiment 27, wherein the disease is a tumor.

[0393] Embodiment 29. The use according to embodiment 28, wherein the tumor is leukemia, lymphoma, multiple myeloma, breast cancer, ovarian cancer, ovarian teratoma, colon cancer, lung cancer, skin cancer, pancreatic cancer, testicular cancer, bladder cancer, uterine cancer, prostate cancer or adrenal cancer.

[0394] Embodiment 30. A method for treating a disease expressing ROR1, comprising administering to a subject in need thereof a therapeutically effective amount of the anti-ROR1 antibody or antigen-binding fragment thereof of any one of embodiments 1-17, the fusion protein of embodiment 22, the antibody-drug conjugate of embodiment 23, the engineered immune effector cell of embodiment 25, or the pharmaceutical composition of embodiment 26.

[0395] Embodiment 31. The method according to embodiment 30, wherein the disease is a tumor.

[0396] Embodiment 32. The method of embodiment 31, wherein the tumor is leukemia, lymphoma, multiple myeloma, breast cancer, ovarian cancer, ovarian teratoma, colon cancer, lung cancer, skin cancer, pancreatic cancer, testicular cancer, bladder cancer, uterine cancer, prostate cancer, or adrenal cancer.

[0397] Embodiment 33. A kit comprising the anti-ROR1 antibody or antigen-binding fragment thereof of any one of embodiments 1-17, the fusion protein of embodiment 22, the antibody-drug conjugate of embodiment 23, the engineered immune effector cell of embodiment 25, or the pharmaceutical composition of embodiment 26.

[0398] For the sake of clarity, the present disclosure is further illustrated by examples, but the examples do not limit the scope of the present disclosure. Those skilled in the art will readily recognize a variety of non-critical parameters that can be changed or modified to produce substantially similar results.

[0399] The UC-961 used in the embodiment is Zilovertamab from Sinovac Biotech. The IgG isotype used in Examples 8 and 10 is human IgG1 antibody (Sino The cell information involved in the embodiments of this disclosure is shown in the following table:

[0400] Example 1: Preparation of ROR1 antigen

[0401] Insert the nucleotide sequence encoding the human ROR1 extracellular domain-human Fc fusion protein (human ROR1ECD-hFc) or human / cynomolgus monkey ROR1ECD-His tag recombinant protein (human / cyno ROR1ECD-His) into the expression vector pcDNA3.1(+) with appropriate restriction enzyme sites. In Expi293 cells (THERMO FISHER Human ROR1ECD-hFc and human / cyno ROR1ECD-His were expressed in a PCR product (Catalog No. 100044202). The amino acid sequence of human ROR1ECD-hFc is shown in SEQ ID NO: 93; the amino acid sequence of human / cyno ROR1ECD-His is shown in SEQ ID NO: 94.

[0402] Example 2: Generation of anti-ROR1 monoclonal antibodies

[0403] Human ROR1ECD-hFc was emulsified with Freund's complete adjuvant or Freund's incomplete adjuvant in a 1:1 volume ratio and administered subcutaneously to immunize A / J mice, BALB / c mice, or SJL mice at a dose of 25 μg / mouse every 2 to 3 weeks for 7-9 weeks. Starting from the second immunization, booster immunizations were performed. Serum was collected one week after each booster immunization, and the antibody titer in the serum was determined by ELISA. Serum with an antibody titer greater than 1:10 was selected. 5 Three days before cell fusion, the mice were injected with human ROR1ECD-hFc without adjuvant for sprint immunization. model: ) The spleen cells from the immunized mice were fused with SP2 / 0 myeloma cells. After fusion, the cells were treated with HAT-containing Catalog number: 21060-017) and serum ( Catalog number: 10099-141C) SFM medium ( Catalog number: 11995-040) was resuspended and added to a 96-well plate at 100 μL / well. After incubation in a 37° C., 5% CO 2 incubator for 7 days, the hybridoma cell culture supernatant was collected for screening of anti-ROR1 monoclonal antibodies.

[0404] Example 3: Screening of anti-ROR1 monoclonal antibodies

[0405] Hybridoma cell culture supernatants were screened by ELISA using human / cyno ROR1 ECD-His to obtain positive clones. Positive clones were subcloned to obtain positive monoclonal clones. Positive monoclonal clones were evaluated by flow cytometry (FACS) using the Jeko-1 cell line, which naturally expresses ROR1. Positive monoclonal clones m3G9B1, m29H5D8, m135A2B10, and m137G11D10 were identified.

[0406] Example 4: Preparation of anti-ROR1 chimeric antibodies

[0407] (1) Obtaining cDNA

[0408] Hybridoma cells m3G9B1, m29H5D8, m135A2B10 and m137G11D10 were selected and total RNA was extracted using a total RNA extraction kit ( Total RNA was isolated from cells (catalog number: 9767) as a template and the kit instructions were followed (THERMO FISHER Catalog number: 18080051) using superscript III reverse transcriptase to synthesize the first-strand cDNA. Using the first-strand cDNA as a template, mouse IgG primers and kappa primers were then used to amplify the variable region sequence of the mouse antibody by PCR reaction. The PCR mixture was separated by electrophoresis in a 1% agarose / Tris-borate gel containing 0.5 μg / mL ethidium bromide. DNA fragments of the expected size were cut from the gel and purified. The purified PCR product was cloned into the pMD-19T vector ( Catalog number: 6013) and transformed into DH5α competent E. coli cells ( Single colonies were picked from the LB solid culture plate for DNA sequencing to obtain the heavy chain variable region and light chain variable region sequences of the anti-ROR1 mouse antibody, as shown in Table 1.

[0409] (2) Construction and expression of chimeric antibodies

[0410] The mouse VL region gene fragment was connected to the human κ chain constant region gene fragment to construct a chimeric light chain expression plasmid, and the mouse VH region gene fragment was connected to the human IgG1 constant region gene fragment to construct a chimeric heavy chain expression plasmid. When the ExpiCHO-S cell density reached 6×10 6 When the expression plasmids of chimeric heavy chain and light chain were expressed in 1:1, the plasmids were co-transfected into ExpiCHO-S cells (THERMO FISHER Protein expression was performed in ExpiCHO Expression Medium (THERMO FISHER Catalog number: A29100-01) was cultured at 37°C with 8% CO2. After 7-10 days of culture, the cells were purified by Protein A column (GE Catalog number: 17-5474-02) to purify chimeric antibodies from cell culture supernatants.

[0411] Table 1. Sequence information of anti-ROR1 mouse antibodies and chimeric antibodies (SEQ ID NO.)

[0412] Note: The VH and VL amino acid sequences of the mouse antibody and the chimeric antibody are the same, and the amino acid sequences and nucleotide sequences of the heavy and light chains are the same as those of the anti-ROR1 chimeric antibody.

[0413] Example 5: In vitro binding activity detection of anti-ROR1 chimeric antibodies

[0414] (1) Surface plasmon resonance (SPR) detection of the binding of anti-ROR1 chimeric antibody to ROR1

[0415] A certain amount of anti-ROR1 antibody was captured by Anti-hIgG chip, and then human / cynomolgus monkey ROR1 protein (Acro Catalog number: RO1-H522y), using The reaction signal was detected in real time to obtain the binding and dissociation curves. The buffer used in the experiment was Universal buffer (137 mM NaCl, 2.7 mM KCl, 10 mM Na2HPO4·12H2O, 1.8 mM KH2PO4, 0.05% surfactant P-20, pH 7.4). Anti-hIgG was coupled to the surface of a CM5 chip to capture the anti-ROR1 chimeric antibody and the benchmark UC-961 ( Catalog number: HY-P99201), and then the signal value of the interaction between different concentrations of ROR1 protein (100nM, 50nM, 25nM, 12.5nM, 6.25nM, 3.125nM) and anti-ROR1 antibody was detected. The flow rate of the flow cell was 50μL / min, the association time was 240s, the dissociation time was 1400s, and it was regenerated with 3M MgCl2 (GE) for 60s. The baseline was stable. The affinity and kinetics 1:1 binding mode calculation results were obtained in the evaluation software, and the affinity results are shown in Table 2.

[0416] Table 2. Binding affinity of anti-ROR1 chimeric antibodies to ROR1

[0417] (2) FACS detection of the binding of anti-ROR1 chimeric antibody to cells

[0418] The cell lines A549, SW620 and Jeko-1 that naturally express ROR1 were cultured at 1×10 5 Cells / well were added to a 96-well plate, and serially diluted anti-ROR1 antibody (starting at 6.67 nM, 5-fold dilution, 7 concentrations) was added and incubated at 4°C for 0.5 h. The 96-well plate was washed with FACS buffer ( Catalog number: 130-091-221) after washing three times, the secondary antibody PE anti-human IgG Fc ( Catalog number: 109-116-170) was diluted 1:200, added to a 96-well plate at 100 μL / well, and incubated at 4°C for 20 min. The cells were washed three times with FACS buffer and analyzed by flow cytometry ( Model: iQue3) Detection and analysis. Analyze data and calculate EC 50 The results are shown in Table 3 and Figures 1A-1C.

[0419] Table 3. Binding EC of anti-ROR1 chimeric antibodies to ROR1-expressing cells 50 and the maximum combined value

[0420] Example 6: Humanization of anti-ROR1 antibodies

[0421] The three antibodies m29H5D8, m135A2B10 and m137G11D10 with better binding activity were selected for humanization. The m29H5D8, m135A2B10 and m137G11D10 antibodies were humanized using the CDR grafting method. Human germline antibody sequences with high homology to the mouse m29H5D8, m135A2B10, and m137G11D10 antibodies were screened, and the complementarity determining regions (CDRs) in the VH and VL of the mouse m29H5D8, m135A2B10, and m137G11D10 antibodies were grafted onto the template human antibody. Several amino acid residues in the framework regions (FR) of the template human antibodies' VH and VL were backmutated to the corresponding amino acid residues in the mouse m29H5D8, m135A2B10, and m137G11D10 antibodies to obtain humanized light and heavy chain variable regions.

[0422] The humanized light chain variable region was linked to the human kappa chain constant region to construct a humanized light chain, and the humanized heavy chain variable region was linked to the human IgG1 constant region to construct a humanized heavy chain. Humanized antibodies were constructed and expressed according to the methods described in Example 4. The sequence information of the anti-ROR1 humanized antibody is shown in Table 4.

[0423] Table 4. Sequence information of anti-ROR1 humanized antibodies (SEQ ID NO.)

[0424] Example 7: Binding activity detection of anti-ROR1 humanized antibodies

[0425] The binding of the humanized anti-ROR1 antibody to ROR1 was detected using SPR, and the binding of the humanized anti-ROR1 antibody to cells naturally expressing ROR1 was detected using FACS. The experimental methods were similar to those in Example 5. The cells used to detect the binding of the humanized anti-ROR1 antibody to cells naturally expressing ROR1 were PA-1, Jeko-1, and SW620. The binding affinity of the humanized anti-ROR1 antibody to ROR1 is shown in Table 5, and the binding affinity of the humanized anti-ROR1 antibody to cells expressing ROR1 is shown in Tables 6-1 to 6-3 and Figures 2A to 2I.

[0426] Table 5. Binding affinity of anti-ROR1 humanized antibodies to ROR1

[0427] Table 6-1. EC binding of anti-ROR1 humanized antibodies to ROR1-expressing cells 50 and the maximum combined value

[0428] Table 6-2. EC binding of anti-ROR1 humanized antibodies to ROR1-expressing cells 50 and the maximum combined value

[0429] Table 6-3. EC binding of anti-ROR1 humanized antibodies to ROR1-expressing cells 50 and the maximum combined value

[0430] Example 8: Internalization of anti-ROR1 humanized antibodies

[0431] The cDNA encoding human ROR1 (SEQ ID NO: 95) was obtained by gene synthesis and then subcloned into the expression vector pcDNA3.1(+). The expression vectors were transfected into NCI-1975, NCI-H1993 and MDA-MB-468 cells according to the instructions of PCR product (catalog number 11668019) to obtain stable cell lines NCI-1975-ROR1, NCI-H1993-ROR1 and MDA-MB-468-ROR1.

[0432] Internalization analysis of anti-ROR1 antibodies was performed based on binding to the stably expressed ROR1 cell lines NCI-1975-ROR1, NCI-H1993-ROR1, and MDA-MB-468-ROR1, using isotype IgG as a negative control. The cell density of ROR1-expressing cells was adjusted to 2 × 10 6 100 μL / mL, add 20 μL / well to 96-well plate. The internalization detection reagent in the catalog number: 90564) was mixed with the anti-ROR1 humanized antibody at a volume ratio of 1:1. For NCI-H1975-ROR1 cells, the final concentration of the anti-ROR1 humanized antibody was 26.7 nM; for NCI-H1993-ROR1 and MDA-MB-468-ROR1 cells, the final concentration of the anti-ROR1 humanized antibody was 5.3 nM. After incubation at 37°C in the dark for 15 minutes, the cells were diluted 5-fold into 6 concentration gradients, and the gradient dilution co-incubation system was added to a 96-well plate at 20 μL / well. The cells were incubated at 37°C for 2-3 hours and analyzed by flow cytometry (Sartorius, model iQue3). The data were analyzed and the EC was calculated. 50The results are shown in Figures 3A-3C, Tables 7-1, and 7-2. These data indicate that hz29H5D8-3.2, hz135A2B10-1.1, and hz137G11D10-2.1 can be effectively internalized in cells expressing ROR1.

[0433] Table 7-1. Internalization of anti-ROR1 humanized antibodies in ROR1-expressing cells

[0434] Table 7-2. Internalization of anti-ROR1 humanized antibodies in ROR1-expressing cells

[0435] Example 9: Inhibitory effect of anti-ROR1 humanized antibodies on the non-canonical Wnt signaling pathway stimulated by Wnt5a

[0436] MEC-1 cells (Nanjing Kebai Biotechnology, catalog number: CBP60514) naturally express Wnt5a, a ligand of ROR1. Based on these cells, the inhibition of the non-canonical Wnt signaling pathway induced by Wnt5a stimulation by anti-ROR1 humanized antibodies was analyzed.

[0437] The cDNA encoding human ROR1 (SEQ ID NO: 95) was obtained by gene synthesis and then subcloned into the expression vector pcDNA3.1(+). The expression vector was transfected into 293T-NF-κB cells according to the instructions of PCR product (catalog number 11668019) to obtain the stable cell line 293T-ROR1-NF-κB.

[0438] The cell density of 293T-ROR1-NF-κB cells stably expressing ROR1 was adjusted to 2×10 5 cells / mL, 100 μL / well was inoculated into a 96-well white plate ( Catalog number: 3917), incubate overnight. Take the 96-well white plate, discard the supernatant, add anti-ROR1 humanized antibody diluted with MEC-1 cell supernatant (final concentration in the plate is 20nM, 10nM, 2.5nM), 100 μL / well, and incubate in a 5% CO2, 37°C incubator for 24h; set the group without antibody as the blank control group. Take Bio-Lite Luciferase Assay System detection reagent ( The cells were equilibrated to room temperature using a 96-well plate (Catalog No. DD1201-03). The above-mentioned detection reagent (100 μL / well) was added to a white 96-well plate. After a 3-minute reaction, the chemiluminescent signal was detected using a multifunctional microplate reader (PE, model Envision 2105). Data were analyzed and inhibition rates were calculated. The results are shown in Figure 4. The results demonstrate that the humanized anti-ROR1 antibodies hz29H5D8-3.2, hz135A2B10-1.1, and hz137G11D10-2.1 all inhibited the Wnt5a-stimulated non-canonical Wnt signaling pathway, and were superior to UC-961.

[0439] Inhibition rate (%) = [(RLU value of blank control group - RLU value of antibody group) / RLU value of blank control group] × 100%

[0440] Example 10: ADCC effect of anti-ROR1 humanized antibody

[0441] Based on the reporter gene method, PA-1 cells were used as target cells and recombinant Jurkat cells (BPS Bioscience TM , catalog number: 60541) to detect the ADCC effect of anti-ROR1 humanized antibody, and the same type IgG was used as a negative control. PA-1 cells were adjusted to a cell density of 2×10 using MEM medium containing 10% FBS. 5 / mL, inoculated into a 96-well all-white plate at 100 μL / well and incubated overnight. Take the 96-well all-white plate, discard the supernatant, add the experimental medium (RPMI-1640 medium containing 2% FBS) and serially diluted anti-ROR1 humanized antibody (with a final concentration of 13.3nM in the plate as the starting concentration, 5-fold serial dilution), 50 μL / well. Recombinant Jurkat cells were adjusted to a cell density of 4×10 using experimental medium. 6 50 μL / well was inoculated into the 96-well white plate and incubated in a 5% CO2, 37°C incubator for 6 h. Catalog number: DD1201-03) equilibrated to room temperature, the above detection reagent was added to a 96-well white plate, 100 μL / well, reacted for 3 minutes, and the chemiluminescent signal was detected using a multifunctional microplate reader. Analyze the data and calculate the EC 50 The ADCC effect of the anti-ROR1 humanized antibody is shown in Figure 5. The calculated EC 50 Shown in Table 8.

[0442] Table 8. ADCC effect of anti-ROR1 humanized antibodies on PA-1 cells

[0443] The sequence information of the present disclosure is summarized in Table S2 below.

[0444] Table S2. Sequence information

[0445] For the purposes of description and disclosure, all patents, patent applications, and other identified publications are expressly incorporated herein by reference. These publications are provided solely for their disclosure prior to the filing date of the present disclosure. All statements regarding the dates of these documents or representations of their contents are based on the information available to the applicant and do not constitute any admission as to the correctness of the dates or contents of these documents. Furthermore, any citation of these publications herein does not constitute an admission that the publications form part of the common general knowledge in the art, in any country.

[0446] Although the present disclosure has been described in detail above using general descriptions and specific embodiments, it will be apparent to those skilled in the art that modifications or improvements may be made based on this disclosure. Therefore, such modifications or improvements, which do not depart from the spirit of this disclosure, are within the scope of protection claimed by this disclosure.

Claims

1. An anti-ROR1 antibody or an antigen-binding fragment thereof, comprising: a HCDR1 comprising the amino acid sequence shown in SEQ ID NO: 25, 1, 9 or 17, a HCDR2 comprising the amino acid sequence shown in SEQ ID NO: 26, 2, 10, 18, 49 or 50, a HCDR3 comprising the amino acid sequence shown in SEQ ID NO: 27, 3, 11 or 19, a LCDR1 comprising the amino acid sequence shown in SEQ ID NO: 28, 4, 12 or 20, a LCDR2 comprising the amino acid sequence shown in SEQ ID NO: 29, 5, 13 or 21, and a LCDR3 comprising the amino acid sequence shown in SEQ ID NO: 30, 6, 14 or 22.

2. The anti-ROR1 antibody or antigen-binding fragment thereof according to claim 1, wherein The anti-ROR1 antibody or antigen-binding fragment thereof comprises: (1) a HCDR1 comprising the amino acid sequence of SEQ ID NO:25, a HCDR2 comprising the amino acid sequence of SEQ ID NO:26, a HCDR3 comprising the amino acid sequence of SEQ ID NO:27, a LCDR1 comprising the amino acid sequence of SEQ ID NO:28, a LCDR2 comprising the amino acid sequence of SEQ ID NO:29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:30; (2) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 1, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 2, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 3, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 4, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 5, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 6; (3) a HCDR1 comprising the amino acid sequence of SEQ ID NO:9, a HCDR2 comprising the amino acid sequence of SEQ ID NO:50, a HCDR3 comprising the amino acid sequence of SEQ ID NO:11, a LCDR1 comprising the amino acid sequence of SEQ ID NO:12, a LCDR2 comprising the amino acid sequence of SEQ ID NO:13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:14; (4) a HCDR1 comprising the amino acid sequence of SEQ ID NO:9, a HCDR2 comprising the amino acid sequence of SEQ ID NO:10, a HCDR3 comprising the amino acid sequence of SEQ ID NO:11, a LCDR1 comprising the amino acid sequence of SEQ ID NO:12, a LCDR2 comprising the amino acid sequence of SEQ ID NO:13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:14; (5) a HCDR1 comprising the amino acid sequence of SEQ ID NO:9, a HCDR2 comprising the amino acid sequence of SEQ ID NO:49, a HCDR3 comprising the amino acid sequence of SEQ ID NO:11, a LCDR1 comprising the amino acid sequence of SEQ ID NO:12, a LCDR2 comprising the amino acid sequence of SEQ ID NO:13, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:14; or (6) HCDR1 comprising the amino acid sequence of SEQ ID NO:17, HCDR2 comprising the amino acid sequence of SEQ ID NO:18, HCDR3 comprising the amino acid sequence of SEQ ID NO:19, LCDR1 comprising the amino acid sequence of SEQ ID NO:20, LCDR2 comprising the amino acid sequence of SEQ ID NO:21, and LCDR3 comprising the amino acid sequence of SEQ ID NO:

22.

3. The anti-ROR1 antibody or antigen-binding fragment thereof according to claim 1 or 2, wherein: The anti-ROR1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region whose amino acid sequence is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence shown in SEQ ID NO: 60, 7, 15, 23, 31, 51, 52, 56, 57, 58 or 61.

4. The anti-ROR1 antibody or antigen-binding fragment thereof according to any one of claims 1 to 3, wherein The anti-ROR1 antibody or antigen-binding fragment thereof comprises a light chain variable region whose amino acid sequence is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence shown in SEQ ID NO:63, 8, 16, 24, 32, 53, 54, 55, 59, 62 or 64.

5. The anti-ROR1 antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, wherein The anti-ROR1 antibody or antigen-binding fragment thereof comprises: (1) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:60, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:63; (2) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:7, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:8; (3) an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, a heavy chain variable region that is at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:16, and a light chain variable region that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:16; (4) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:23, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:24; (5) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:31, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:32; (6) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:51, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:53; (7) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:51, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:54; (8) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:51, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:55; (9) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:52, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:53; (10) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:52, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:54; (11) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:52, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:55; (12) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:56, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:59; (13) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:57, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:59; (14) a heavy chain variable region whose amino acid sequence is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:58, and a heavy chain variable region whose amino acid sequence is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:

59. a light chain variable region that is 95%, 96%, 97%, 98%, 99% or 100% identical; (15) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:60, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:62; (16) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:60, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:64; (17) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:61, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:62; (18) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:61, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:63; or (19) a heavy chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:61, and a light chain variable region having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:

64.

6. The anti-ROR1 antibody or antigen-binding fragment thereof according to any one of claims 1 to 5, wherein The antigen-binding fragment is a Fab fragment, a F(ab')2 fragment, a Fd fragment, a Fv fragment, an isolated CDR region or a scFv; Optionally, the anti-ROR1 antibody or antigen-binding fragment thereof is murine, chimeric or humanized; Optionally, the anti-ROR1 antibody is of IgG1, IgG2, IgG3 or IgG4 isotype.

7. The anti-ROR1 antibody or antigen-binding fragment thereof according to any one of claims 1 to 6, wherein The anti-ROR1 antibody comprises a heavy chain whose amino acid sequence is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence shown in SEQ ID NO:83, 33, 37, 41, 45, 65, 67, 75, 77, 79 or 85.

8. The anti-ROR1 antibody or antigen-binding fragment thereof according to any one of claims 1 to 7, wherein The anti-ROR1 antibody comprises a light chain whose amino acid sequence is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence shown in SEQ ID NO:89, 35, 39, 43, 47, 69, 71, 73, 81, 87 or 91.

9. The anti-ROR1 antibody or antigen-binding fragment thereof according to any one of claims 1 to 8, wherein The anti-ROR1 antibody comprises: (1) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:83, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:89; (2) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:33, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:35; (3) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:37, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:39; (4) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:41, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:43; (5) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:45, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:47; (6) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:65, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:69; (7) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:65, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:71; (8) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:65, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:73; (9) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:67, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:69; (10) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:67, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:71; (11) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:67, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:73; (12) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:75, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:81; (13) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:77, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:81; (14) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:79, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:81; (15) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:83, and an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:

83. 87 having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of 87; (16) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:83, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:91; (17) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:85, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:87; (18) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:85, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:89; or (19) a heavy chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:85, and a light chain having an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:

91.

10. The anti-ROR1 antibody or antigen-binding fragment thereof according to any one of claims 1 to 9, wherein The anti-ROR1 antibody or antigen-binding fragment thereof has one or more of the following properties: (1) Binding to human ROR1; preferably, measured by surface plasmon resonance, with K D binds human ROR1 at 5E-08M or less, 1E-09M or less, or 5E-10M or less; (2) Binding to monkey ROR1; preferably, measured by surface plasmon resonance, with K D binds human ROR1 at 5E-08M or less, 1E-09M or less, or 5E-10M or less; (3) inhibiting the non-classical Wnt signaling pathway stimulated by Wnt5a; preferably, the anti-ROR1 antibody or antigen-binding fragment thereof has an inhibition rate of 10% or more, 15% or more, or 20% or more on the non-classical Wnt signaling pathway stimulated by Wnt5a at a concentration of 20 nM; (4) plays an internalization role in cells expressing ROR1; (5) exert ADCC effect on cells expressing ROR1; (6) inducing regression of tumor growth in vivo; and (7) Delaying tumor growth in vivo.

11. An isolated nucleic acid comprising a nucleotide sequence encoding the anti-ROR1 antibody or antigen-binding fragment thereof according to any one of claims 1 to 10.

12. A method for preparing the anti-ROR1 antibody or antigen-binding fragment thereof according to any one of claims 1 to 10, comprising culturing a host cell comprising the nucleic acid according to claim 11 to express the anti-ROR1 antibody or antigen-binding fragment thereof, and separating and purifying the anti-ROR1 antibody or antigen-binding fragment thereof in a system. 13 . An antibody-drug conjugate comprising the anti-ROR1 antibody or antigen-binding fragment thereof according to any one of claims 1 to 10.

14. A pharmaceutical composition comprising the anti-ROR1 antibody or antigen-binding fragment thereof according to any one of claims 1 to 10 or the antibody-drug conjugate according to claim 13, and one or more pharmaceutically acceptable excipients.

15. A method for treating a disease expressing ROR1, comprising administering to a subject in need thereof a therapeutically effective amount of the anti-ROR1 antibody or antigen-binding fragment thereof according to any one of claims 1 to 10, the antibody-drug conjugate according to claim 13, or the pharmaceutical composition according to claim 14; Preferably, the disease is a tumor; Preferably, the tumor is leukemia, lymphoma, multiple myeloma, breast cancer, ovarian cancer, ovarian teratoma, colon cancer, lung cancer, skin cancer, pancreatic cancer, testicular cancer, bladder cancer, uterine cancer, prostate cancer or adrenal cancer.

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