T cell-targeted delivery vehicles

Abstract

The present disclosure provides delivery particles comprising: (a) a targeting moiety on the surface of the particle, wherein the targeting moiety comprises an antibody or an antigen-binding fragment thereof that binds to a T cell antigen selected from CD5, CD7, and CD27; and (b) a payload encapsidated within the particle. The disclosure provides methods of using the particles.

Description

Attorney Docket No.: AZL-004WOT CELL-TARGETED DELIVERY VEHICLESCROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U. S. Provisional Application No. 63 / 760,866, filed February 20, 2025. which is hereby incorporated in its entirety by reference.SEQUENCE LISTING

[0002] The instant application contains a Sequence Listing which has been submitted via Patent Center and is hereby incorporated by reference in its entirety'. Said XML copy, created on Month XX, 20XX, is named XXXXXUS_sequencelisting.xml, and is X, XXX. XXX bytes in size.BACKGROUND

[0003] CRISPR / Cas systems are revolutionizing the field of gene editing and genome engineering. Efficient methods for delivering CRISPR-Cas genome editing components into target cells are needed, for both ex vivo and in vivo applications. Cunent delivery’ strategies have drawbacks, including delivery systems that result in low editing efficiencies or off-target editing.

[0004] Additional systems and methods for increasing targeted delivery’ of CRISPR / Cas systems are needed.SUMMARY

[0005] In one aspect provided is a delivery' particle comprising (a) a targeting moiety on the surface of the particle, wherein the targeting moiety comprises one or more antibody or antigenbinding fragments thereof that bind to one or more T cell antigens selected from the group consisting of: CD3, CD5, CD7, CD4, CD28, TCR and CD27; and (b) a payload encapsidated within the particle.

[0006] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1. CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 86, and a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 87.

[0007] In an embodiment, the CDR-H 1 comprises the sequence set forth in SEQ ID NO: 136, CDR-H2 comprises the sequence set forth in SEQ ID NO: 137, CDR-H3 comprises the sequence set forth in SEQ ID NO: 138, CDR-L1 comprises the sequence set forth in SEQ ID NO: 139. CDR-L2 comprises the sequence set forth in SEQ ID NO: 140, and CDR-L3 comprises the sequence set forth in SEQ ID NO: 141, according to Kabat; or (b) the CDR-H1 comprises the sequence set forth in SEQ ID NO: 142, CDR-H2 comprises the sequence set forth1IPTS / 200318117.8Attorney Docket No.: AZL-004WOin SEQ ID NO: 143, CDR-H3 comprises the sequence set forth in SEQ ID NO: 144, CDR-L1 comprises the sequence set forth in SEQ ID NO: 145, CDR-L2 comprises the sequence set forth in SEQ ID NO: 146, and CDR-L3 comprises the sequence set forth in SEQ ID NO: 147, according to Chothia; or (c) the CDR-H1 comprises the sequence set forth in SEQ ID NO: 148, CDR-H2 comprises the sequence set forth in SEQ ID NO: 149. CDR-H3 comprises the sequence set forth in SEQ ID NO: 150, CDR-L1 comprises the sequence set forth in SEQ ID NO: 151, CDR-L2 comprises the sequence set forth in SEQ ID NO: 152, and CDR-L3 comprises the sequence set forth in SEQ ID NO: 153, according to IMGT; or (d) the CDR-H1 comprises the sequence set forth in SEQ ID NO: 154, CDR-H2 comprises the sequence set forth in SEQ ID NO: 155, CDR-H3 comprises the sequence set forth in SEQ ID NO: 156, CDR-L1 comprises the sequence set forth in SEQ ID NO: 157, CDR-L2 comprises the sequence set forth in SEQ ID NO: 158, and CDR-L3 comprises the sequence set forth in SEQ ID NO: 159, according to North.

[0008] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising a VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 86, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 87.

[0009] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 86, and the VL sequence set forth in SEQ ID NO: 87.

[0010] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising an scFv at least 90%. 91%. 92%. 93%. 94%. 95%. 96%. 97%. 98%. 99%. or 100% identical to a sequence set forth in SEQ ID NO: 16 or 15.

[0011] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the scFv sequence set forth in SEQ ID NO: 16 or 15.

[0012] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 86, and a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1. CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 87, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 86 and SEQ ID NO: 87, respectively; or the antibody or antigen-binding2IPTS / 200318117.8Attorney Docket No.: AZL-004WOfragment thereof specifically binds CD3 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 72, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1. CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 73, optionally wherein CDR-H1, CDR-H2. CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat. as shown in SEQ ID NO: 72 and SEQ ID NO: 73, respectively; or the antibody or antigenbinding fragment thereof specifically binds CD3 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 74, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 75, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 74 and SEQ ID NO: 75, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 76, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 77, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-LL CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 76 and SEQ ID NO: 77, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 78, and a VL chain sequence comprising three light chain CDR sequences, CDR-LL CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 79, optionally wherein CDR-H1, CDR-H2, CDR-H3. CDR-LL CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 78 and SEQ ID NO: 79, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 80, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 81, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 80 and SEQ ID NO: 81, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 82, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 83. optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-LL CDR-L2, and CDR-L33IPTS / 200318117.8Attorney Docket No.: AZL-004WOare according to Kabat, as shown in SEQ ID NO: 82 and SEQ ID NO: 83, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a VEI chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 84, and a VL chain sequence comprising three light chain CDR sequences. CDR-L1. CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 85, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 84 and SEQ ID NO: 85, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD4 and comprises a VH chain sequence comprising three heavy’ chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 88, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 89, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 88 and SEQ ID NO: 89, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD28 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 90, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 91. optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1. CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 90 and SEQ ID NO: 91, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD28 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2. and CDR-H3, of the VH sequences set forth in SEQ ID NO: 92, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 93, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-Ll, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 92 and SEQ ID NO: 93, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD28 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 94, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 95, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1. CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 94 and SEQ ID NO: 95, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 96, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the4IPTS / 200318117.8Attorney Docket No.: AZL-004WOVL sequences set forth in SEQ ID NO: 97, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 96 and SEQ ID NO: 97, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl. CDR-H2, and CDR-H3. of the VH sequences set forth in SEQ ID NO: 98, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 99, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 98 and SEQ ID NO: 99. respectively; or the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 100, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 101, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-LL CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 100 and SEQ ID NO: 101, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl. CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 100, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2. and CDR-L3, of the VL sequences set forth in SEQ ID NO: 102, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 100 and SEQ ID NO: 102, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl. CDR-H2, and CDR-H3. of the VH sequences set forth in SEQ ID NO: 103, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 104, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 103 and SEQ ID NO: 104, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 105, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 101, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-LL CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 105 and SEQ ID NO: 101, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl. CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 105, and a VL chain5IPTS / 200318117.8Attorney Docket No.: AZL-004WOsequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 102, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 105 and SEQ ID NO: 102, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD7 and comprises a VH chain sequence comprising three heavy chain CDR sequences. CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 106, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 107, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-LL CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 106 and SEQ ID NO: 107, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD7 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 108, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 109, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 108 and SEQ ID NO: 109, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl. CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 110, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 111, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 110 and SEQ ID NO: 111, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 112, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 113, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-LL CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 112 and SEQ ID NO: 113, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-HL CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 114, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 115, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 114 and SEQ ID NO: 115, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-6IPTS / 200318117.8Attorney Docket No.: AZL-004WOHl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 116, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 117, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1. CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 116 and SEQ ID NO: 117, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 118, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 119. optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 118 and SEQ ID NO: 119, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl. CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 120, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 121, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 120 and SEQ ID NO: 121, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 122, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 123, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-LL CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 122 and SEQ ID NO: 123, respectively; or the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 124, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 125. optionally wherein CDR-H1, CDR-H2, CDR-H3. CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 124 and SEQ ID NO: 125, respectively; or the antibody or antigen-binding fragment thereof specifically binds TCR and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl. CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 126, and a VL chain sequence comprising three light chain CDR sequences, CDR-LL CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 127, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 126 and SEQ ID NO: 127, respectively; or the antibody or antigen-binding fragment thereof specifically binds7IPTS / 200318117.8Attorney Docket No.: AZL-004WOTCR and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 128, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 129, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1. CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 128 and SEQ ID NO: 129, respectively; or the antibody or antigen-binding fragment thereof specifically binds TCR and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 130, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 129, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 130 and SEQ ID NO: 129, respectively; or the antibody or antigen-binding fragment thereof specifically binds TCR and comprises a VH chain sequence comprising three heavy chain CDR sequences. CDR-Hl. CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 131, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 129, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 131 and SEQ ID NO: 129, respectively; or the antibody or antigen-binding fragment thereof specifically binds TCR and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 132, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 133, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-LL CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 132 and SEQ ID NO: 133, respectively; or the antibody or antigen-binding fragment thereof specifically binds TCR and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl. CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 134, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2. and CDR-L3, of the VL sequences set forth in SEQ ID NO: 133, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 134 and SEQ ID NO: 133, respectively; or the antibody or antigen-binding fragment thereof specifically binds TCR and comprises a VH chain sequence comprising three heavy chain CDR sequences. CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 135, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 133, optionally wherein CDR-H1, CDR-H2, CDR-H3,8IPTS / 200318117.8Attorney Docket No.: AZL-004WOCDR-LL CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 135 and SEQ ID NO: 133, respectively.

[0013] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 86, and the VL sequence set forth in SEQ ID NO: 87; or the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 72. and the VL sequence set forth in SEQ ID NO: 73; or the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 74, and the VL sequence set forth in SEQ ID NO: 75; or the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 76, and the VL sequence set forth in SEQ ID NO: 77; or the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 78, and the VL sequence set forth in SEQ ID NO: 79; or the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 80, and the VL sequence set forth in SEQ ID NO: 81; or the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 82, and the VL sequence set forth in SEQ ID NO: 83; or the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 84, and the VL sequence set forth in SEQ ID NO: 85; or the antibody or antigen-binding fragment thereof specifically binds CD4 comprising the VH sequence set forth in SEQ ID NO: 88, and the VL sequence set forth in SEQ ID NO: 89; or the antibody or antigen-binding fragment thereof specifically binds CD28 comprising the VH sequence set forth in SEQ ID NO: 90, and the VL sequence set forth in SEQ ID NO: 91; or the antibody or antigen-binding fragment thereof specifically binds CD28 comprising the VH sequence set forth in SEQ ID NO: 92. and the VL sequence set forth in SEQ ID NO: 93; or the antibody or antigen-binding fragment thereof specifically binds CD28 comprising the VH sequence set forth in SEQ ID NO: 94, and the VL sequence set forth in SEQ ID NO: 95; or the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence set forth in SEQ ID NO: 96, and the VL sequence set forth in SEQ ID NO: 97; or the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence set forth in SEQ ID NO: 98, and the VL sequence set forth in SEQ ID NO: 99; or the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence set forth in SEQ ID NO: 100, and the VL sequence set forth in SEQ ID NO: 101; or the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence set forth in SEQ ID NO: 100, and the VL sequence set forth in SEQ ID NO: 102; or the antibody or antigen-binding fragment thereof specifically binds CD59IPTS / 200318117.8Attorney Docket No.: AZL-004WOcomprising the VH sequence set forth in SEQ ID NO: 103, and the VL sequence set forth in SEQ ID NO: 104; or the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence set forth in SEQ ID NO: 105, and the VL sequence set forth in SEQ ID NO: 101; or the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence set forth in SEQ ID NO: 105, and the VL sequence set forth in SEQ ID NO: 102; or the antibody or antigen-binding fragment thereof specifically binds CD7 comprising the VH sequence set forth in SEQ ID NO: 106, and the VL sequence set forth in SEQ ID NO: 107; or the antibody or antigen-binding fragment thereof specifically binds CD7 comprising the VH sequence set forth in SEQ ID NO: 108, and the VL sequence set forth in SEQ ID NO: 109; or the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 110, and the VL sequence set forth in SEQ ID NO: 111; or the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 112, and the VL sequence set forth in SEQ ID NO: 113; or the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 114, and the VL sequence set forth in SEQ ID NO: 115; or the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 116, and the VL sequence set forth in SEQ ID NO: 117; or the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 118, and the VL sequence set forth in SEQ ID NO: 119; or the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 120, and the VL sequence set forth in SEQ ID NO: 121; or the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 122, and the VL sequence set forth in SEQ ID NO: 123; or the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 124, and the VL sequence set forth in SEQ ID NO: 125; or the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence set forth in SEQ ID NO: 126, and the VL sequence set forth in SEQ ID NO: 127; or the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence set forth in SEQ ID NO: 128, and the VL sequence set forth in SEQ ID NO: 129; or the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence set forth in SEQ ID NO: 130, and the VL sequence set forth in SEQ ID NO: 129; or the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence set forth in SEQ ID NO: 131, and the VL sequence set forth in SEQ ID NO: 129; or the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence set forth in SEQ ID NO: 132, and the VL sequence set forth in10IPTS / 200318117.8Attorney Docket No.: AZL-004WOSEQ ID NO: 133; or the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence set forth in SEQ ID NO: 134, and the VL sequence set forth in SEQ ID NO: 133; or the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence set forth in SEQ ID NO: 135, and the VL sequence set forth in SEQ ID NO: 133.

[0014] In an embodiment, (a) the antibody or antigen-binding fragment thereof specifically binds CD3 comprising an scFv having the sequence set forth in SEQ ID NOs: 16, 15, or 3-14; or (b) the antibody or antigen-binding fragment thereof specifically binds CD5 comprising an scFv having the sequence set forth in SEQ ID NOs: 24-37; or (c) the antibody or antigen-binding fragment thereof specifically binds CD7 comprising an scFv having the sequence set forth in SEQ ID NOs: 38-40; or (d) the antibody or antigen-binding fragment thereof specifically binds CD27 comprising an scFv having the sequence set forth in SEQ ID NOs: 42-57; or (e) the antibody or antigen-binding fragment thereof specifically binds CD4 comprising an scFv having the sequence set forth in SEQ ID NOs: 17-18; or (f) the antibody or antigen-binding fragment thereof specifically binds CD28 comprising an scFv having the sequence set forth in SEQ ID NOs: 19-23; or (g) the antibody or antigen-binding fragment thereof specifically binds TCR comprising an scFv having the sequence set forth in SEQ ID NOs: 58-71.

[0015] In one aspect provided is a delivery particle comprising: (a) a targeting moiety on the surface of the particle, wherein the targeting moiety comprises a means for binding a T cell antigen; and (b) a payload encapsidated within the particle.

[0016] In one aspect provided is a delivery' particle comprising: (a) a targeting moiety on the surface of the particle, wherein the targeting moiety comprises a means for binding a T cell antigen selected from the group consisting of: CD3. CD5. CD7. CD4, CD28. TCR and CD27; and (b) a payload encapsidated within the particle.

[0017] In an embodiment, the particle further comprises a pseudotyping protein on the surface of the particle, optionally wherein the pseudotyping protein comprises a pseudotyping viral envelope protein further optionally wherein the pseudotyping viral envelope protein is a VSVg protein or variant thereof.

[0018] In an embodiment, the particle is selected from a lipid nanoparticle (LNP) or a virus like particle (VLP).

[0019] In an embodiment, the VLP is a retrovirus-derived particle.

[0020] In an embodiment, the payload is selected from a gene editing system, a polynucleotide encoding a transgene, a peptide, and a detectable marker.11IPTS / 200318117.8Attorney Docket No.: AZL-004WO

[0021] In an embodiment, the gene editing system comprises (i) a fusion protein comprising a Gag polyprotein and a Cas endonuclease, optionally wherein the Cas endonuclease is fused to the C-terminus of the Gag polyprotein; and (ii) a guide RNA.

[0022] In one aspect provided is a virus like particle (VLP) comprising (a) a targeting moiety on the surface of the particle, wherein the targeting moiety comprises an antibody or an antigenbinding fragment thereof that binds to a T cell antigen selected from CDS, CD7, and CD27; (b) a pseudotyping viral envelope protein; (c) a gene-editing system encapsidated within the VLP: and (d) a polynucleotide encoding a transgene.

[0023] In an embodiment, (a) the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 96, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2. and CDR-L3, of the VL sequences set forth in SEQ ID NO: 97, optionally wherein CDR-HL CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 96 and SEQ ID NO: 97, respectively; or (b) the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1. CDR-H2, and CDR-H3. of the VH sequences set forth in SEQ ID NO: 98, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 99, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 98 and SEQ ID NO: 99, respectively; or (c) the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 100, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2. and CDR-L3, of the VL sequences set forth in SEQ ID NO: 101, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1. CDR-L2. and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 100 and SEQ ID NO: 101, respectively; or (d) the antibody or antigenbinding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 100. and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 102, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 100 and SEQ ID NO: 102, respectively; or (e) the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain12IPTS / 200318117.8Attorney Docket No.: AZL-004WOsequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 103, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 104, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 103 and SEQ ID NO: 104, respectively; or (!) the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 105, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3. of the VL sequences set forth in SEQ ID NO: 101, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 105 and SEQ ID NO: 101, respectively; or (g) the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences. CDR-H1, CDR-H2. and CDR-H3, of the VH sequences set forth in SEQ ID NO: 105, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 102, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-Ll, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 105 and SEQ ID NO: 102. respectively; or (h) the antibody or antigen-binding fragment thereof specifically binds CD7 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 106, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 107, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-LL CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 106 and SEQ ID NO: 107, respectively; or (i) the antibody or antigen-binding fragment thereof specifically binds CD7 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 108, and a VL chain sequence comprising three light chain CDR sequences, CDR-LL CDR-L2. and CDR-L3, of the VL sequences set forth in SEQ ID NO: 109, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 108 and SEQ ID NO: 109, respectively; or (j) the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 110, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 111, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ13IPTS / 200318117.8Attorney Docket No.: AZL-004WOID NO: 110 and SEQ ID NO: 111, respectively; or (k) the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 112, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2. and CDR-L3, of the VL sequences set forth in SEQ ID NO: 113, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 112 and SEQ ID NO: 113, respectively; or (1) the antibody or antigenbinding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 114, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 115, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 114 and SEQ ID NO: 115, respectively; or (1) the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 116, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 117, optionally wherein CDR-HL CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 116 and SEQ ID NO: 117, respectively; or (m) the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy' chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 118, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 119, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 118 and SEQ ID NO: 119, respectively; or (n) the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 120, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 121, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 120 and SEQ ID NO: 121, respectively; or (o) the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 122, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2,14IPTS / 200318117.8Attorney Docket No.: AZL-004WOand CDR-L3, of the VL sequences set forth in SEQ ID NO: 123, optionally wherein CDR-HL CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 122 and SEQ ID NO: 123, respectively; or (p) the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences. CDR-H1, CDR-H2, and CDR-H3. of the VH sequences set forth in SEQ ID NO: 124, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 125, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2. and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 124 and SEQ ID NO: 125, respectively.

[0024] In one aspect provided is a virus like particle (VLP) comprising (a) a targeting moiety on the surface of the particle, wherein the targeting moiety comprises a means for binding to a T cell antigen selected from CD5, CD7, and CD27; (b) a pseudotyping viral envelope protein; (c) a gene-editing system encapsidated within the VLP; and (d) a polynucleotide encoding a transgene.

[0025] In one aspect provided is a method of delivering a payload to a population of target cells comprising contacting the population of target cells with the particle as defined in any of the embodiments described herein, wherein the population of target cells expresses a T cell antigen selected from CD5, CD7, and CD27.

[0026] In an embodiment, the delivery efficiency of the particle is greater than 20%, greater than 30%, greater than 40%, or greater than 50%.

[0027] In an embodiment, the delivery efficiency of the particle is at least 5% higher than the delivery efficiency of a particle comprising one or more targeting moieties that bind to CD4, CD3, and / or CD28.

[0028] In one aspect provided is a method of editing a population of target cells comprising contacting the population of target cells with the particle as defined in any of the embodiments described herein, wherein the population of target cells expresses a T cell antigen selected from CD5, CD7, and CD27.

[0029] In an embodiment, the editing efficiency of the particle is greater than 20%, greater than 30%, greater than 40%, or greater than 50%.

[0030] In an embodiment, the editing efficiency of the particle is at least 5% higher than the editing efficiency of a particle comprising one or more targeting moieties that bind to CD4, CD3, and / or CD28.15IPTS / 200318117.8Attorney Docket No.: AZL-004WO

[0031] In one aspect provided is a method of modifying a population of target cells to express a transgene comprising contacting the population of target cells with the particle as defined in any of the embodiments described herein, wherein the population of target cells expresses a T cell antigen selected from CD5, CD7, and CD27.

[0032] In an embodiment, the integration efficiency of the particle is at least 7%.

[0033] In an embodiment, the integration efficiency of the particle is at least 2% higher than the integration efficiency of a particle comprising one or more targeting moieties that bind to CD4, CD3. and / or CD28.

[0034] In one aspect provided is a method of delivering a payload to a population of target cells comprising contacting the population of target cells with a particle comprising: (a) a targeting moiety on the surface of the particle, comprising means for binding human CD5; and (b) a payload encapsidated within the particle, wherein the delivery’ efficiency of the particle is at least 5% higher than the delivery efficiency a particle comprising one or more targeting moieties that bind to CD4, CD3, and / or CD28.

[0035] In one aspect provided is a method of delivering a payload to a population of target cells comprising contacting the population of target cells with a particle comprising: (a) a targeting moiety on the surface of the particle, comprising means for binding human CD7; and (b) a payload encapsidated within the particle, wherein the delivery’ efficiency of the particle is at least 5% higher than the delivery efficiency a particle comprising one or more targeting moieties that bind to CD4, CD3, and / or CD28.

[0036] In one aspect provided is a method of delivering a payload to a population of target cells comprising contacting the population of target cells with a particle comprising: (a) a targeting moiety on the surface of the particle, comprising means for binding human CD27; and (b) a payload encapsidated within the particle, wherein the delivery’ efficiency of the particle is at least 5% higher than the delivery efficiency a particle comprising one or more targeting moieties that bind to CD4, CD3, and / or CD28.BRIEF DESCRIPTION OF THE DRAWINGS

[0037] These and other features, aspects, and advantages of the present invention will become better understood with regard to the following description, and accompanying drawings, where:

[0038] FIG. 1 shows the expression of surface markers measured by flow cytometry on Jurkat cells.16IPTS / 200318117.8Attorney Docket No.: AZL-004WO

[0039] FIG. 2 shows a schematic of the procedure for assessing delivery and editing of target cells by scFv-targeted delivery particles.

[0040] FIG. 3 shows the expression of surface markers measured by flow cytometry on engineered HEK293T cells.

[0041] FIG. 4 shows a schematic of the scFv-targeted Cas9- delivery particles.

[0042] FIG. 5A and FIG. 5B show the percent integration (FIG. 5A) and editing (FIG. 5B) of scFv-targeted Cas9-delivery particles on Jurkat cells.

[0043] FIG. 6A and FIG. 6B show the percent integration (FIG. 6A) and editing (FIG. 6B) of scFv-targeted Cas9- delivery particles on HEK293T cells.

[0044] FIG. 7A - FIG. 7F show the percent integration with a dose titration of T cell-targeting scFv Cas9- delivery particles in Jurkats.

[0045] FIG. 8A - FIG. 8F show the percent editing with a dose titration of T cell-targeting scFv Cas9- delivery particles in Jurkats.

[0046] FIG. 9A - FIG. 9F show the percent integration with a dose titration of T cell-targeting scFv Cas9- delivery particles in human-ligand expressed HEK293Ts.

[0047] FIG. 10A - FIG. 10F show the percent editing with a dose titration of T cell-targeting scFv Cas9- delivery particles in human-ligand expressed HEK293Ts.

[0048] FIG. 11A and FIG. 11B show the percent integration in HEK293T cells expressing cyno NHP ligands and pig-tailed NHP ligands with a dose titration of the T-cell targeting scFv Cas9-delivery particles.

[0049] FIG. 12A and FIG. 12B show the percent editing in HEK293T cells expressing cyno NHP ligands and pig-tailed NHP ligands with a dose titration of the T-cell targeting scFv Cas9-delivery particles.

[0050] FIG. 13 shows effects of TCR-targeted and CD3-targeted delivery particles on the activation and editing in resting human T cells.

[0051] FIG. 14 shows effects of TCR-targeted and CD3-targeted delivery particles on the activation and editing in activated human T cells.

[0052] FIG. 15 shows effects of CD3-targeted delivery particles on the activation and editing in resting human and NHP T cells.17IPTS / 200318117.8Attorney Docket No.: AZL-004WO

[0053] FIG. 16 A - FIG. 16F show the percentage of CD 19+ B cells (FIG. 16A-FIG. 16C) and percentage of CAR+ T cells (FIG. 16D-FIG. 16F) in mouse blood and spleen following treatment with CD3-targeted delivery particles and AAV expressing CAR.DETAILED DESCRIPTION

[0054] For the purposes of promoting an understanding of the principles of the present disclosure, reference will now be made to preferred embodiments and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the disclosure is thereby intended, such alteration and further modifications of the disclosure as illustrated herein, being contemplated as would normally occur to one skilled in the art to which the disclosure relates.

[0055] The present disclosure provides delivery particles comprising a targeting moiety that binds to a T cell antigen on the surface of the particle and a pay load encapsidated within the particle. Inclusion of the T cell targeting moiety7directs the particle to the target cell (e.g., a T cell) and minimizes off-target delivery.Delivery Particles

[0056] The present disclosure provides delivery^ particles comprising: (a) a targeting moiety on the surface of the particle, wherein the targeting moiety7comprises an antibody or an antigenbinding fragment thereof that binds to a T cell antigen; and (b) a pay load encapsidated within the particle.

[0057] Herein, “delivery particle" refers to a microscopic structure engineered or naturally occurring, designed to encapsulate, protect, and transport active payloads (e.g., nucleic acids, proteins, drugs, or other therapeutic molecules) to target cells or tissues. Delivery7particles are characterized by their ability7to efficiently traverse biological barriers (e.g., cell membranes), maintain stability in biological environments, and enable controlled release of their pay load at the intended site of action. In some embodiments, the delivery7particle is selected from the group consisting of virus-like particles (VLPs), exosome, liposomes, and lipid nanoparticles (LNPs). In some embodiments, the delivery7particle is a VLP wherein the VLP is a retrovirus-derived particle (e.g., a lentivirus derived particle).

[0058] As used herein, the terms “virus like particle” (VLP) and “enveloped delivery7vehicle” (EDV) are synonymous and refer to a polymer structure including viral proteins, such an envelope protein, and a lipid membrane. Delivery particles (e.g., a VLP) may be used to deliver one or more cargo molecules to a cell. Generally for delivery particles (e.g., a VLP) described herein, a delivery7particle (e.g., a VLP) also includes a targeting molecule (e.g., any of the18IPTS / 200318117.8Attorney Docket No.: AZL-004WOtargeting molecules described herein) that provides for specific binding to a target cell, thereby facilitating delivery of its cargo a particular target cell. In some cases, delivery particles (e.g., a VLP) are used to encapsidate or otherwise carry a cargo protein, for example, a polynucleotide-guided nuclease. In instances where the cargo protein is a polynucleotide-guided nuclease, the delivery particles (e.g.. a VLP) may also encapsidate a guide polynucleotide. In some cases, delivery particles (e.g., a VLP) are used to encapsidate nucleic acids, for example, a nucleic acid with a coding sequence for a protein of interest, e.g, a polynucleotide-guided nuclease.Examples of delivery' particles (e.g., a VLP) can be found in Hamilton, Jennifer R et al.“Targeted delivery of CRISPR-Cas9 and transgenes enables complex immune cell engineering.” Cell reports vol. 35,9 (2021): 109207.; Hamilton, Jennifer R et al. “In vivo human T cell engineering with enveloped delivery7vehicles.” Nature Biotechnology, 10.1038 / s41587-023-02085-z. 11 Jan. 2024, doi:10.1038 / s41587-023-02085-z; and U. S. Patent Application Publication No. 2022 / 0403379.

[0059] The term “vector” refers to a vehicle for introducing a cargo molecule, e.g., nucleic acids, proteins, small molecules, or combinations thereof, into a target cell. In some embodiments, the nucleic acids, proteins, small molecules, or combinations thereof are packaged within the vector. In some embodiments, a vector is a polynucleotide that encodes a cargo molecule. In some embodiments, a vector is also used for the integration of a nucleotide sequence (e.g., a gene or a coding sequence) into a target nucleic acid of the target cell, and optionally, for the expression of the nucleotide sequence (e.g., a gene or a coding sequence) by that cell. Vector forms include, for example, plasmids or virus-based nucleic-acid vectors (e.g., a retroviral or a lentiviral genome), as well polymer particles, enveloped delivery7vehicles (EDVs), and lipid nanoparticles (LNPs).

[0060] Delivery7particles (e.g., a VLP) can include a Gag polyprotein (or processed subdomains thereof), which can be present as part of a fusion with another component, such as a polynucleotide-guided nuclease and / or a targeting polyprotein. In general, a native Gag polyprotein includes (1) a matrix (MA) polypeptide that binds to cell membranes and directs viral particles (e.g., VLPs) to the cell surface, (2) a capsid (CA) polypeptide that forms an inner shell of a viral particle (e.g., VLPs), and (3) a nucleocapsid (NC) polypeptide that binds directly to viral genomic material (e.g., RNA). A Gag precursor can be expressed from viral genomic RNA as a single polypeptide that is later proteolytically cleaved to produce an MA polypeptide, a capsid polypeptide, and an NC polypeptide that are each separate from the others. A native gag polyprotein also contains (1) a p2 polypeptide between the CA and NC polypeptides that plays a role in ordered virus assembly and infectivity, (2) a pl polypeptide between the NC polypeptide19IPTS / 200318117.8Attorney Docket No.: AZL-004WOand a p6 polypeptide that may play a role in virus infectivity, and (3) a p6 polypeptide that plays a role in the late steps of viral replication. Gag proteins are discussed in detail in Olson, Erik D, and Karin Musier-Forsyth. “Retroviral Gag protein-RNA interactions: Implications for specific genomic RNA packaging and virion assembly.” Seminars in cell & developmental biology vol.86 (2019): 129-139. doi: 10.1016 / j.semcdb.2018.03.015; Hill. Melissa K et al. “Proline residues within spacer peptide pl are important for human immunodeficiency virus type 1 infectivity, protein processing, and genomic RNA dimer stability.” Journal of virology vol. 76,22 (2002): 11245-53. doi: 10.1128 / jvi.76.22.11245-11253.2002; Schmalen. Adrian et al. “The N-Terminus of the HIV-1 p6 Gag Protein Regulates Susceptibility to Degradation by IDE.” Viruses vol. 10,12710. 12 Dec. 2018, doi: 10.3390 / vl 0120710; Newman, John L et al. “Flexibility in the P2 domain of the HIV-1 Gag polyprotein.” Protein science: a publication of the Protein Society vol.13,8 (2004): 2101-7. doi: 10.1110 / ps.04614804.

[0061] A Gag polyprotein can be derived from a lentiviral Gag polyprotein or a retroviral Gag polyprotein. For example, the lentiviral Gag polyprotein can be selected from the group consisting of a bovine immunodeficiency virus Gag polyprotein, a simian immunodeficiency virus Gag polyprotein, a feline immunodeficiency virus Gag polyprotein, a human immunodeficiency virus (HIV) Gag polyprotein, an equine infection anemia virus Gag polyprotein, and a caprine arthritis encephalitis virus Gag polyprotein. A Gag polyprotein can be Rous Sarcoma Virus (RSV) Gag polyprotein or a Moloney Leukemia Virus (MLV) Gag polyprotein. In some embodiments, the Gag protein is derived from an HIV Gag polyprotein, such as an HIV-1 Gag polyprotein.

[0062] The polypeptides of the Gag polyprotein can each be of a different origin and the polypeptides may be combined in a single synthetic Gag polyprotein fragment.

[0063] An HIV-1 Gag polyprotein generally includes each of the following subdomains, from N- to C-terminus: a MA polypeptide, a CA polypeptide, a p2 polypeptide, an NC polypeptide, a pi polypeptide, and a p6 polypeptide. Accordingly, in an illustrative non-limiting example, a Gag polyprotein is a HIV-1 Gag polyprotein that includes each the following subdomains: from N- to C-terminus: a MA polypeptide, a CA polypeptide, a p2 polypeptide, an NC polypeptide, a pi polypeptide, and a p6 polypeptide with each of their respective native protease cleavage sites between each subdomain.

[0064] A Gag polyprotein can include Gag polyproteins where one or more native peptide linkers between the encoded subdomains are modified, e.g., where a native protease cleavage site is modified to be a heterologous protease cleavage site (e.g., a protease cleavage site typically found linking other subdomains within a Gag polyprotein or a protease cleavage site20IPTS / 200318117.8Attorney Docket No.: AZL-004WOfrom a virus other than the virus from which the subdomains are derived). A Gag polyprotein can be a HIV-1 Gag polyprotein that includes each of the following subdomains: a MA polypeptide, a CA polypeptide, a p2 polypeptide, an NC polypeptide, a pi polypeptide, and a p6 polypeptide, and wherein the HIV gag polyprotein includes one or more heterologous protease cleavage sites between one or more of: i) the MA polypeptide and the CA polypeptide; li) the CA polypeptide and the p2 polypeptide; iii) the p2 polypeptide and the NC polypeptide; iv) the NC polypeptide and the pi polypeptide; and v) the pi polypeptide and the p6 polypeptide.Exemplary Gag polyproteins are disclosed in WO 2020 / 102709.

[0065] In some embodiments, a delivery' particle (e.g., a VLP) includes a Gag polyprotein and a heterologous protein (e.g., a CRISPR-Cas9 endonuclease) in a single polypeptide (i.e., a fusion protein). In some embodiments, a delivery particle (e.g., a VLP) includes a heterologous protein that is a polynucleotide-guided nuclease for delivery' to a target cell.

[0066] In some embodiments, a delivery' particle (e.g., a VLP) includes a Gag-Cas9 fusion polypeptide, wherein at least a fractional proportion of the Cas9 nuclease molecules within the delivery' particle (e.g., a VLP) is operably linked to the C-terminus of a Gag polyprotein.

[0067] In general, Gag fusion proteins provided herein include a protease cleavage sequence that links a Gag polyprotein to a heterologous protein (e.g., a polynucleotide-guided nuclease, such as a Cas9 endonuclease). In general, a protease cleavage sequence is located C-terminal of the nuclear export sequence(s) and N-terminal of the heterologous protein and / or nuclear localization signal(s) within the fusion proteins described herein. Exemplary cleavage sites can be derived from an HIV-1 protease cleavage site, a TEV cleavage site, a PreScission cleavage site, a human rhinovirus 3C protease cleavage site, an enterokinase cleavage site, an Epstein-Barr virus protease cleavage site, a cathepsin D cleavage site, and / or a thrombin cleavage site, or any combination thereof. Further cleavage sites are disclosed in W02020102709 and US Patent Pub. No. 20220403379, all of which are hereby incorporated by reference in their entirety'. In some embodiments, a protease cleavage sequence is linked to an adjacent protein element or domain through a peptide linker (e.g, a glycine-serine based linker). In some embodiments, a protease cleavage site includes the amino acid sequence SQNYPIVQ.

[0068] In some embodiments, a delivery’ particle (e.g., a VLP) includes a Pol polyprotein and / or processed domains thereof. A Pol polyprotein can be expressed from a Gag-Pol gene, including an HIV-1 Gag-Pol gene. In some embodiments, the processed domains of the Pol polyprotein includes a protease domain, a reverse transcriptase domain, and an integrase, which can be subsequently processed during maturation into separate domains.21IPTS / 200318117.8Attorney Docket No.: AZL-004WO

[0069] In some embodiments, a Pol polyprotein includes inactivating mutations in the integrase domain (e.g., aD64 mutation, such as D64V). In some embodiments, a Pol polyprotein includes inactivating mutations in both the reverse transcriptase domain (e.g., a D185 mutation, such as DI 85) and the integrase domain (e.g., a D64 mutation, such as D64V). In some embodiments, a Pol polyprotein includes inactivating mutations in the reverse transcriptase domain (e.g.. a D185 mutation, such as DI 85 A). EDVs with a Pol polyprotein includes inactivating mutations in the reverse transcriptase domain are generally limited to delivery particles (e.g., VLPs) that deliver a cargo molecule, such as a polynucleotide-guided nuclease (e.g., a Cas9 endonuclease) without the need for reverse transcription of a cargo.

[0070] In some embodiments, a Pol polyprotein includes a full or partial deletion in the reverse transcriptase domain. In some embodiments, a Pol polyprotein includes a full or partial deletion in the integrase domain. In some embodiments, a Pol polyprotein includes a full or partial deletions in both the reverse transcriptase domain and the integrase domain.

[0071] In some embodiments, a Gag polyprotein includes an HIV-1 Gag polyprotein and / or a Pol polyprotein includes an HIV-1 Pol polyprotein. In some embodiments, a Gag polyprotein includes an HIV-1 Gag polyprotein and a Pol polyprotein includes an HIV-1 Pol polyprotein.

[0072] As used herein, the terms “lipid particle,” “lipid nanoparticle,” and “LNP” refer to a particle comprising lipids and may comprise phospholipids and / or ionizable lipids. An LNP may comprise additional lipid components, such as a sterol and / or a conjugated lipid, and may further comprise a nucleic acid, wherein the nucleic acid may be encapsulated within the LNP. In some embodiments, the LNP also comprises a polynucleotide-guided nuclease and / or a guide RNA within the LNP.

[0073] In some embodiments, the particles comprise a pseudotyping protein on the surface of the particle. In some embodiments, the pseudotyping protein is a pseudotyping viral envelope protein, such as a fusogenic viral glycoprotein. In some embodiments, the pseudotyping viral envelope protein is a VSVg protein or variant thereof. Variant VSVg proteins with improved functionally over WT VSVg are known in the art. See e.g., WO 2019 / 057974, describing VSVg variants comprising K47 and K354 substitutions; WO 2022 / 183072 and WO 2023 / 114884, describing mutations at position 182; and WO 2024 / 1079959 - describing various truncation and deletion variants of VSVg. Each of these references are incorporated herein by reference.

[0074] Pseudotyping viral envelope protein can include a fusogenic viral glycoprotein variants. In some embodiments, a fusogenic viral glycoprotein variant includes a VSV-G variant including mutations that reduce or eliminate VSV-G binding to its native cognate binding22IPTS / 200318117.8Attorney Docket No.: AZL-004WOpartner LDL receptor. Without wishing to be bound by theory, reduced binding to an LDL-receptor may reduce serum neutralization of VLPs with VSV-G. VSV-G variants can include a K47Q mutation and / or a R354A mutation. Without wishing to be bound by theory7, a K47Q mutation and / or a R354A mutation reduce VSV-G binding to an LDL receptor without appreciably disrupting the fusogenic activity of VSV-G. For example, without wishing to be bound by theory, an VLP that uses both a targeting molecule (e.g, an anti-CD3 scFv) and a VSV-G variant can specifically bind to a cell of interest (e.g, bind CD3 on a T cell) and then VSV-G mediates fusion of the VLP with the cell membrane (e.g., the T cell membrane). In some embodiments, the fusogenic viral glycoprotein variant includes a VSV-G variant including a K47Q mutation. In some embodiments, the fusogenic viral glycoprotein variant includes a VSV-G variant including a R354A mutation. In some embodiments, the fusogenic viral glycoprotein variant includes a VSV-G variant including a K47Q mutation and a R354A mutation.

[0075] In some embodiments, the VSV-G variant includes a chimeric VSV-G. Chimeric VSV-G proteins can include chimeras that combine the properties of resistance to serum neutralization with a higher level of fusogenic activity. In some embodiments, the chimeric VSV-G includes an Indiana VSV-G domain (the Indiana strain is generally considered to have a higher level of fusogenic activity relative to VSV-G of other strains) and a Cocal VSV-G domain (the Cocal strain is generally considered to have higher resistance to human serum neutralization relative to VSV-G of other strains).

[0076] A VSVg variant can have the amino acid sequence MKCLLYLAFLFIGVNCKFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQ VKMPQSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTK QGTWLNPGFPPQSCGYATVTDAEAVIVQVTPHHVLVDEYTGEWVDSQFINGKCSNYIC PTVHNSTTWHSDYKVKGLCDSNLISMDITFFSEDGELSSLGKEGTGFRSNYFAYETGGK ACKMQYCKHWGVRLPSGVWFEMADKDLFAAARFPECPEGSSISAPSQTSVDVSLIQDV ERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAA PILSRMVGMISGTTTEAELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSD LHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIG LIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK (SEQ ID NO: 160)

[0077] In some embodiments, the VSV-G variant includes the amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to the sequence as set forth in SEQ ID NO: 160. In some embodiments, the VSV-G variant includes the amino acid sequence as set forth in SEQ ID NO: 160.23IPTS / 200318117.8Attorney Docket No.: AZL-004WO

[0078] A VSVg variant can have the amino acid sequence MKCLLYLAFLFIGVNCKFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQ VKMPQSHKAIQADGWMCHAAKWITTCDFRWYGPKYITHSIHSIQPTSEQCKESIKQTKQ GTWMSPGFPPQNCGYATVTDSVAVVVQATPHHVLVDEYTGEWIDSQFPNGKCETEEC ETVHNSTVWYSDYKVTGLCDATLISMDITFFSEDGELSSLGKEGTGFRSNYFAYETGGK ACKMQYCKHWGVRLPSGVWFEMADKDLFAAARFPECPEGSSISAPSQTSVDVSLIQDV ERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAA PILSRMVGMISGTTTEAELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSD LHLSSKAQVFEHPHLAEAPKQLPEEETLFFGDTGISKNPVELIEGWFSSWKSTVVTFFFAI GVFILLYVVARIVIAVRYRYQGSNNKRIYNDIEMSRFRK(SEQ ID NO: 161).

[0079] In some embodiments, the chimeric VSV-G variant includes the amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to the sequence as set forth in SEQ ID NO: 161. In some embodiments, the chimeric VSV-G includes the amino acid sequence as set forth in SEQ ID NO: 161.

[0080] A delivery7particle (e.g., a VLP) can have a targeting molecule and a fusogenic viral protein with reduced off-target binding (e.g., a VSV-G variant including a K47Q mutation and a R354A mutation with reduced bind to an LDL receptor) such that fusion is favored for target cells expressing the cognate specific cell surface molecule of the targeting molecule.Payloads

[0081] In general, the delivery particles provided herein encapsidate a payload. A payload can be a nucleic acid, protein, small molecule, or a combination thereof. In some embodiments, a payload is selected from a gene editing system, a polynucleotide encoding a transgene, a peptide, and a detectable marker.

[0082] In some embodiments, the payload is a nucleic acid payload. In some embodiments, the nucleic acid encodes a transgene (e.g., a CAR, an engineered TCR, an antibody). In some embodiments, the nucleic acid is non-encoding (e.g., a gRNA or siRNA). In some embodiments, the nucleic acid payload is a lentiviral genome comprising a nucleic acid encoding a transgene flanked by long-terminal repeats (LTRs). Nucleic acid that encode a transgene payload can include a homology-directed repair template. The term “homology-directed repair’1or “HDR” refers to a cellular process in which cut or nicked ends of a DNA strand e.g., a genome) are repaired by polymerization from a nucleic acid template (an “HDR template”) that includes sequences that are homologous to the cut or nicked DNA strand (“homology arms”). Thus, the original sequence is replaced with a sequence on the HDR template. An HDR template (e.g., with an exogenous transgene flanked by regions of homologous sequences) can be introduced 24IPTS / 200318117.8Attorney Docket No.: AZL-004WOinto a cell to obtain a specific HDR-induced change of the sequence at a target site. Particles with such payloads are described in the art, see WO 2020 / 102709, incorporated herein by reference.

[0083] A HDR template polynucleotide generally includes a sequence or sequences that flank a payload-encoding nucleotide sequence with sufficient homology' to a sequence at the target site (e.g., at a target locus on genomic DNA. such as a T cell receptor alpha constant region (TRAC) locus) to support homology-directed repair between the HDR template polynucleotide and the target site which the homology' arms have complementarity. Such sequences with sufficient homology' are known in the art as “homology7arms."’ Typically', a HDR template polynucleotide includes two homology7arms, each flanking an insertion sequence (e.g.. a sequence encoding a heterologous polypeptide, such as a transgene, i.e., a payload-encoding nucleotide sequence). Homology arms can contain at least 95%, at least 99%, or 100% homology with the nucleotide sequences flanking the target site, e.g., from 30 to 50 bases, from 15 to 30 bases, from 10 to 15 bases, or from 5 to 10 bases adjacent to or immediately flanking the target site and / or nuclease-directed cleavage site. Each homology arm can include at least 50 nucleotides, at least 100 nucleotides, at least 150 nucleotides, at least 200 nucleotides, at least 250 nucleotides, at least 300 nucleotides, at least 350 nucleotides, at least 400 nucleotides, at least 450 nucleotides, at least 500 nucleotides, at least 550 nucleotides, at least 600 nucleotides, at least 650 nucleotides, at least 700 nucleotides, at least 750 nucleotides, at least 800 nucleotides, at least 850 nucleotides, at least 900 nucleotides, at least 950 nucleotides, at least 1000 nucleotides (or any integral value betw een 10 and 1500 nucleotides or more) of sequence homology with the sequence of a target site (e.g., a target locus on genomic DNA) so long as it can support homology -directed repair (e.g., for gene insertion, gene deletion, gene disruption, or gene modification). Each homology arm can include between 100-700 nucleotides. Each homology arm can include between 600-800 nucleotides. Each homology arm can include between 650-750 nucleotides. Each homology7arm can include about 700 nucleotides. Each homology7arm can include 700 nucleotides. Each homology7arm can include between 200-1000 nucleotides. Each homology7arm can include between 200-400 nucleotides. Each homology arm can include between 200-700 nucleotides.

[0084] A target locus can be an exon. A target locus can be an intron. A target locus can be an intron / exon boundary (i. e., a portion of at least one of the homology' arms is complementary to an intron and a portion of the other homology arms is complementary7to an exon).

[0085] In some embodiments, the payload is a polyprotein. In some embodiments, the polyprotein is a polynucleotide-guided nuclease, an antibody, or peptide drug. In some25IPTS / 200318117.8Attorney Docket No.: AZL-004WOembodiments, a polynucleotide-guided nuclease is an RNA-guided nuclease. In some embodiments, the RNA-guided nuclease is a CRISPR / Cas enzyme or a fusion protein comprising a CRISPR / Cas enzyme. Suitable CRISPR / Cas enzy mes are described in detail below. For example, in some cases, the CRISPR / Cas enzy me is a type II CRISPR / Cas enzyme. In some cases, the type II CRISPR / Cas enzyme is a Cas9 polypeptide. In some cases, the CRISPR / Cas enzyme is a type V CRISPR / Cas effector polypeptide, e.g., Casl2a, Casl2b, Casl2c, Casl2d, or Casl2e. In some cases, the CRISPR / Cas enzyme is atype VI CRISPR / Cas effector polypeptide, e.g., Casl3a, Casl3b, Casl3c, or Casl3d. In some cases, the CRISPR / Cas enzyme is a Casl4 polypeptide, e.g.. Casl4a, a Casl4b. or Casl4c. Also suitable for use is a variant CRISPR / Cas effector polypeptide, where the variant CRISPR / Cas polypeptide has reduced nucleic acid cleavage activity.

[0086] In some embodiments, the payload comprises one or more CRISPR-Cas guide nucleic acids, where the one or more CRISPR-Cas guide nucleic acids provide for knockout of an endogenous nucleic acid.

[0087] In some embodiments, the CRISPR / Cas enzyme is a variant CRISPR / Cas enzyme with reduced or no nucleic acid cleavage activity. In some embodiments, the CRISPR / Cas enzyme is fused to a protein or nucleic acid modifying enzyme. In some embodiments, the protein or nucleic acid modifying enzyme is a base editor. In some embodiments, the base editor is a cytidine deaminase. In some embodiments, the base editor is an adenosine deaminase. In some embodiments, the protein or nucleic acid modify ing enzyme is a prime editor, wherein a variant CRISPR / Cas enzyme with reduced or no nucleic acid cleavage activity is fused to a reverse transcriptase.

[0088] In some embodiments, the nuclease is a homing nuclease polypeptide; a Fokl polypeptide; a transcription activator-like effector nuclease (TALEN) polypeptide; a MegaTAL polypeptide; a meganuclease polypeptide; a zinc finger nuclease (ZFN); an ARCUS nuclease; and the like. The meganuclease can be engineered from an LADLIDADG homing endonuclease (LHE). A megaTAL polypeptide can comprise a TALE DNA binding domain and an engineered meganuclease. See, e.g., WO 2004 / 067736 (homing endonuclease); Umov et al. (2005) Nature 435:646 (ZFN); Mussolino et al. (2011) Nucl. Acids Res. 39:9283 (TALE nuclease); Boissel et al. (2013) Nucl. Acids Res. 42:2591 (MegaTAL).

[0089] In some embodiments, one or more payloads can be encapsidated in the delivery particle. For example, in some embodiments, a payload may comprise a nucleic acid and a protein. For example, the pay load may comprise a CRISPR / Cas enzyme and one or more gRNAs (e.g.. a gene editing system). In some embodiments, the payload may comprise a CRISPR / Cas enzyme 26IPTS / 200318117.8Attorney Docket No.: AZL-004WOand a nucleic acid encoding a transgene (e.g, a CAR, engineered TCR, or antibody), such as a HDR template. In some embodiments, a delivery particle (e.g., a VLP) comprises a gag polyprotein that is covalently linked to the CRISPR / Cas enzyme as a single polypeptide (i.e., a fusion protein). Particles with such payloads are described in the art, see WO 2020 / 102709, incorporated herein by reference.

[0090] Polynucleotide-guided nucleases (e.g. a Cas9 endonuclease) can form a ribonucleoprotein (RNP) complex with a guide polynucleotide. Accordingly, a payload can include a RNP complex. For example, a sgRNA can complex with a Cas9 endonuclease to form an RNP complex that is encapsidated within a delivery particle (e.g., a VLP). In general, complexing into an RNP can occur during production of a delivery particle (e.g., a VLP) itself or later complex within the mature delivery particle, or both. In some embodiments, such as those where a polynucleotide-guided nuclease (e.g., a Cas9 endonuclease) is originally expressed as a fusion protein with Gag, a delivery7particle includes an encapsidated RNP complex that includes a released form of the polynucleotide-guided nuclease e.g., follow ing proteolytic cleavage of a protease cleavage site linking the polynucleotide-guided nuclease to the Gag polyprotein.Targeting Moieties

[0091] Described herein are delivery7particles (e.g., VLPs) that include a targeting moiety. A targeting moiety has specific binding for a molecule that is expressed on the surface of a target cell, e.g, a cell-specific binding molecule. Without wishing to be bound by theory, by recognizing cell surface molecule(s) on a target cell, delivery of a pay load (e.g., a genomeediting molecule) can be improved, e.g., by improving specificity7for the target cell. Thus, a delivery7particle (e.g., a VLP) can bind specifically to a target cell, thereby delivering a payload (e.g., genome-editing molecules such as polynucleotide-guided nucleases, with or without guide polynucleotides) to the target cell.

[0092] In some embodiments, the targeting moiety is an antibody or an antibody fragment that binds to the molecule on the target cell, e.g., an scFv, a diabody, a tnabody, a nanobody, and any antigen-binding fragment including the VH and VL domains of an antibody. In some embodiments, the targeting polypeptide is a bispecific antibody. In some embodiments, the targeting polypeptide is an antibody analog, e.g., an affibody, an affilin, an affimer, an affitin, an abody, an anticalin, an avimer, a DARPin, a Fynomer, a Kunitz domain peptide, a monobody, a repebody, a VLR, and a nanoCLAMP. In some embodiments, the targeting polypeptide is a natural ligand of the molecule on the target cell, e.g., a cytokine.

[0093] In some embodiments, the delivery particles (e.g., a VLP) includes a targeting moiety' extended from the surface of the delivery7particles (e.g., a VLP). In some embodiments, the 27IPTS / 200318117.8Attorney Docket No.: AZL-004WOtargeting moiety includes an antigen binding domain capable of specifically binding a cellsurface marker on a target cell. In some embodiments, the delivery particles (e.g., a VLP) includes a cell-specific binding molecule extended from the surface of the delivery particles (e.g., a VLP). In some embodiments, the cell-specific binding molecule includes an antigen binding domain capable of specifically binding a cell-surface marker on a target cell.

[0094] In some embodiments, the target cell is an immune cell, such as a T cell, a B cell, a natural killer (NK) cell, a mast cell, a dendritic cell, a macrophage, a monocyte, and other immune cell types.

[0095] The term "‘T cell’’ refers to a lymphoid cell that typically has undergone maturation in the thymus and generally expresses a T cell receptor molecule and / or other T cell signaling molecules (e.g., the CD3 family member of proteins).. T cells include, but are not limited to, naive T cells, stimulated T cells, primary’ T cells (e.g.. uncultured), cultured T cells, immortalized T cells, helper T cells, cytotoxic T cells, memory T cells, regulatory T cells, natural killer T cells, combinations thereof, or sub-populations thereof. T cells can be CD4+, CD8+, or CD4+ and CD8+. T cells can be helper cells, for example helper cells of type Thl, Th2, Th3, Th9. Th 17, or TFH. T cells can be cytotoxic T cells. Regulatory T cells can be FOXP3+ or FOXP3-. T cells can be a / Beta T cells or gamma / delta T cells. In some embodiments, the T cell is aCD4+CD25hlCD12710regulatory T cell. In some embodiments, the T cell is a regulatory T cell selected from the group consisting of Tri, Th3, CD8+CD28-, Tregl7, and Qa-1 restricted T cells, or a combination or sub-population thereof. In some embodiments, the T cell is a FOXP3+ T cell. In some embodiments, the T cell is a CD4+CD25loCD127hleffector T cell. In some embodiments, the T cell is aCD4 CD25loCD127hiCD45RAhiCD45RO- naive T cell. T cells can include T cells that have been engineered to reduce or eliminate expression of a native T cell receptor molecule, for example, T cells with a CAR or other protein inserted into the TRAC locus that disrupts expression of a native T cell receptor. T cells with reduced or eliminated expression of a native T cell receptor are generally still capable of mediating T cell responses through other T cell signaling molecules (e.g., the CD3 family member of proteins) and a non-native receptor (e.g., a CAR).

[0096] In some embodiments, the T cell antigen is selected from CD3, CD4, CD28, a T cell receptor (TCR), CD5, CD7, and CD27. In some embodiments, the targeting moiety’ is an antibody or fragment thereof, e.g., an scFv or Fab. In some embodiments, the targeting moiety is an scFv. Antibodies and fragments thereof that bind CD3, CD4, CD28, TCR, CD5, CD7, and CD27 are known in the art. For example, WO 2020 / 102709, US 2022-0403379, and WO28IPTS / 200318117.8Attorney Docket No.: AZL-004WO2024 / 044557 describe deliver}’ particles (e.g., a VLP) comprising CD3, CD4, and CD28 targeting moieties. The CD3 / CD4 / CD28 triple targeting moiety was used as a benchmark for assaying the additional targeting moieties described herein. As shown throughout the examples, the ability of a particular targeting moiety to improve targeted delivery of the delivery particles (e.g.. a VLP) compared to these previously described targeting moieties is unpredictable.

[0097] In some embodiments, the targeting moiety includes an antigen binding domain capable of specifically binding a T cell antigen, optionally wherein the T cell antigen is CD3.

[0098] In some embodiments, the targeting moiety includes an anti-CD3 antibody or fragment thereof, e.g., an anti-CD3 scFv or anti-CD3 Fab.

[0099] In some embodiments, the targeting moiety includes an antigen binding domain capable of specifically binding a T cell antigen, optionally wherein the T cell antigen is CD5.

[0100] In some embodiments, the targeting moiety includes an antigen binding domain capable of specifically binding a T cell antigen, optionally wherein the T cell antigen is CD7.

[0101] In some embodiments, the targeting moiety includes an antigen binding domain capable of specifically binding a T cell antigen, optionally wherein the T cell antigen is CD27.

[0102] In some embodiments, the targeting moiety includes an antigen binding domain capable of specifically binding a T cell antigen, optionally wherein the T cell antigen is CD4.

[0103] In some embodiments, the targeting moiety includes an antigen binding domain capable of specifically binding a T cell antigen, optionally wherein the T cell antigen is CD28.

[0104] In In some embodiments, the targeting moiety’ includes an antigen binding domain capable of specifically binding a T cell antigen, optionally wherein the T cell antigen is TCR.

[0105] In some embodiments, the targeting moiety includes a means for binding CD3, e.g., an anti-CD3 scFv or anti-CD3 Fab.

[0106] In some embodiments, the targeting moiety includes a means for binding CD5, e.g., an anti-CD5 scFv or anti-CD5 Fab.

[0107] In some embodiments, the targeting moiety includes a means for binding CD7, e.g., an anti-CD7 scFv or anti-CD7 Fab.

[0108] In some embodiments, the targeting moiety includes a means for binding CD27, e.g.. an anti-CD27 scFv or anti-CD27 Fab.

[0109] In some embodiments, the targeting moiety includes a means for binding CD4, e.g., an anti-CD4 scFv or anti-CD4 Fab.29IPTS / 200318117.8Attorney Docket No.: AZL-004WO

[0110] In some embodiments, the targeting moiety includes a means for binding CD28, e.g., an anti-CD28 scFv or anti-CD28 Fab.

[0111] In some embodiments, the targeting moiety includes a means for binding TCR, e.g., an anti-TCR scFv or anti-TCR Fab.

[0112] In some embodiments, the targeting moiety is an antibody or antibody fragment thereof. The terms "antibody" and “immunoglobulin” are used interchangeably and include an intact immunoglobulin molecule comprising four polypeptide chains: two heavy' chains and two light chains connected by disulfide bonds. Immunoglobulins can be of any isotype. " Antibody fragments" comprise a portion of an intact antibody, for example, the antigen binding or variable region of the intact antibody. Examples of antibody fragments include Fab, Fab', F(ab')2, and Fv fragments; scFv; diabodies; linear antibodies (Zapata et al., Protein Eng. 8(10): 1057-1062 (1995)); domain antibodies (dAb; Holt et al. (2003) Trends Biotechnol. 21:484); single-chain antibody molecules; and multi-specific antibodies formed from antibody fragments. The antibodies and fragments thereof can be further conjugated to other moieties, such as members of specific binding pairs, e.g., biotin (member of biotin- avidin specific binding pair), and the like.

[0113] " Single-chain Fv" or “scFv” antibody fragments comprise the VH and VL domains of antibody, wherein these domains are present in a single polypeptide chain. In some embodiments, the scFv polypeptide further comprises a polypeptide linker between the VH and VL domains, which enables the scFv to form the desired structure for antigen binding. For a review of scFv, see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg and Moore eds., Springer -Verlag, New York, pp. 269-315 (1994).

[0114] As used herein, the term “specifically binds” to a target refers to a binding reaction whereby, for example, a targeting moiety binds to the target with greater affinity, greater avidity, and / or greater duration than it binds to a different target. In some embodiments, a targeting moiety has at least 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 20-fold, 25-fold, 50-fold, 100-fold, 1,000-fold, 10,000-fold, or greater affinity for the target compared to an unrelated target when assayed under the same binding affinity assay conditions. The term “specific binding,” “specifically binds to,” or “is specific for” a particular target, as used herein, can be exhibited, for example, by a molecule (e.g., a ligand) having an equilibrium dissociation constant, KD, for the target of, e.g., 10'2M or smaller, e.g., 10'3M, 10'4M, 10'5M, 10'6M, 10'7M, 10'8M, 10'9M, 10’10M, 10'11M, or 10'12M. In some embodiments, a targeting moiety has a KD of less than 100 nM or less than 10 nM.30IPTS / 200318117.8Attorney Docket No.: AZL-004WO

[0115] In some embodiments, the targeting moieties described herein demonstrated improved delivery of particles comprising the same to target cells, as compared to particles comprising previously described targeting moieties. In some embodiments, the targeting moieties described herein demonstrate an on-target delivery efficiency that is at least 5% higher than particles comprising previously described targeting moieties. In some embodiments, the targeting moieties described herein demonstrate an on-target delivery efficiency that is at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 100% higher than particles comprising previously described targeting moieties. On-target delivery efficiency can be measured by fluorescent reporter assays (e.g., wherein target cells are engineered to express a first fluorescent protein and wherein the particles comprise a second fluorescent protein). Efficiency is measured as the percentage of cells in the target population that express both the first and second fluorescent proteins at the completion of the assay.

[0116] In some embodiments, the targeting moieties described herein demonstrated improved editing efficiency as compared to particles comprising previously described targeting moieties. In such embodiments, the delivery particle comprises one or more components of a gene editing system (e.g., a nuclease such as a CRISPR / Cas enzyme, TALEN, etc., or gRNA). In some embodiments, the targeting moieties described herein demonstrate an editing efficiency that is at least 5% higher than particles comprising previously described targeting moieties. In some embodiments, the targeting moieties described herein demonstrate an editing efficiency that is at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 100% higher than particles comprising previously described targeting moieties. Editing efficiency can be determined by the percentage of cells in a population that comprise a genetic edit (e.g., as determined by the specificity of a gRNA / Cas cargo).

[0117] In some embodiments, the targeting moieties described herein demonstrated improved on-target editing efficiency as compared to particles comprising previously described targeting moieties. In such embodiments, the delivery particle comprises one or more components of a gene editing system (e.g., a nuclease such as a CRISPR / Cas enzyme, TALEN, etc., or gRNA). In some embodiments, the targeting moieties described herein demonstrate an on-target editing efficiency that is at least 5% higher than particles comprising previously described targeting moieties. In some embodiments, the targeting moieties described herein demonstrate an on-31IPTS / 200318117.8Attorney Docket No.: AZL-004WOtarget editing efficiency that is at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 100% higher than particles comprising previously described targeting moi eties. On-target editing efficiency can be determined using a fluorescent reporter assay, wherein target cells are engineered to express a fluorescent protein. On-target editing efficiency is then determined by the percentage of cells in a population that comprise a genetic edit (e.g., as determined by the specificity of a gRNA / Cas cargo) and are positive for the fluorescent protein.

[0118] In some embodiments, the targeting moieties described herein demonstrated improved integration efficiency as compared to particles comprising previously described targeting moieties. In such embodiments, the particle comprises a polynucleotide that can be integrated into the genome of the target cell (e.g., a lentiviral genome encoding a protein or a homology directed repair template). In some embodiments, the targeting moieties described herein demonstrate an integration efficiency that is at least 2% higher than particles comprising previously described targeting moieties. In some embodiments, the targeting moieties described herein demonstrate an integration efficiency that is at least 5% higher than particles comprising previously described targeting moieties. In some embodiments, the targeting moieties described herein demonstrate an integration efficiency that is at least 7% higher than particles comprising previously described targeting moieties. In some embodiments, the targeting moieties described herein demonstrate an integration efficiency that is at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 100% higher than particles comprising previously described targeting moieties. Integration efficiency can be determined by the percentage of cells in a population that comprise the polynucleotide payload integrated into the genome of the target cell.

[0119] In some embodiments, the targeting moieties described herein demonstrated improved on-target integration efficiency as compared to particles comprising previously described targeting moieties. In such embodiments, the particle comprises a polynucleotide that can be integrated into the genome of the target cell (e.g., a lentiviral genome encoding a protein or a homology directed repair template). In some embodiments, the targeting moieties described herein demonstrate an on-target integration efficiency that is at least 5% higher than particles comprising previously described targeting moieties. In some embodiments, the targeting moieties described herein demonstrate an on-target integration efficiency that is at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at32IPTS / 200318117.8Attorney Docket No.: AZL-004WOleast 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 100% higher than particles comprising previously described targeting moieties. On-target editing integration can be determined using a fluorescent reporter assay, wherein target cells are engineered to express a fluorescent protein. On-target integration efficiency is then determined by the percentage of cells in a population that comprise the integrated polynucleotide payload (e.g., as determined by the specificity of a gRNA / Cas cargo) and are positive for the fluorescent protein.

[0120] In some embodiments, the targeting moieties described herein comprise an antigenbinding domain (e.g., an scFv) and one or more domains that facilitate the antigen-binding domain extending from a membrane surface (e.g., from the surface of a delivery particle (e.g., a VLP), such as a stalk and / or transmembrane domain. The CD8a stalk and transmembrane domain sequences are provided in the table below.

[0121] In some embodiments, the targeting moieties described herein comprise an antigenbinding domain (e.g., an scFv), a CD8a stalk (e.g., SEQ ID NO: 1), and a CD8a transmembrane domain (e.g., SEQ ID NO: 2). The CD8a stalk and transmembrane domain sequences are provided in the table below.Domain AA Sequence SEQ ID NO: CD8a stalk TTTPAPRPPTPAPTIASQPLSLRPEACRPAAG 1GAVHTRGLDFACD CD8a IYIWAPLAGTCGVLLLSLVITLYC 2 transmembranedomain

[0122] In some embodiments, the targeting moiety comprises an scFv that binds to CD3 (“a CD3 scFv”). In some embodiments, the CD3 scFv is based on an antibody selected from UCHT, Acapatamab, OKT3, FN-18, and SP34-2 (See Sen et al. Automated Antibody De Novo Sequencing and Its Utility in Biopharmaceutical Discovery. J Am Soc Mass Spectrom. 2017 May;28(5): 803-810, incorporated herein by reference in its entirety). In some embodiments, the CD3 scFv comprises, from N-terminus to C-terminus, VH domain - linker - VL domain. In some embodiments, the scFv comprises, from N-terminus to C-terminus, VL domain - linker -VH domain.

[0123] In some embodiments, the targeting moiety comprises an scFv that binds to CD5 (“a CD5 scFv’'). In some embodiments, the CD5 scFv is based on an antibody selected from those 33IPTS / 200318117.8Attorney Docket No.: AZL-004WOdescribed in WO 2016 / 172606, incorporated herein by reference in its entirety. In some embodiments, the CD5 scFv comprises, from N-terminus to C-terminus, VH domain - linker -VL domain. In some embodiments, the scFv comprises, from N-terminus to C-terminus, VL domain - linker - VH domain.

[0124] In some embodiments, the targeting moiety comprises an scFv that binds to CD7 (“a CD7 scFv”). In some embodiments, the CD7 scFv is based on an antibody selected from those described in WO 2003 / 051926, incorporated herein by reference in its entirety. In some embodiments, the CD7 scFv comprises, from N-terminus to C-terminus, VH domain - linker -VL domain. In some embodiments, the scFv comprises, from N-terminus to C-terminus, VL domain - linker - VH domain.

[0125] In some embodiments, the targeting moiety comprises an scFv that binds to CD27 (“a CD27 scFv”). In some embodiments, the CD27 scFv is based on an antibody selected from M2177, H2191, M2191, (see the exapsy.org / abcd database entries for ABCD_AG335, _336, and _337, respectively), varlilumab, 3C2 (See WO 2019 / 204462, incorporated herein by reference in its entirety ), 2B3 (See WO 2019 / 204462, incorporated herein by reference in its entirety ), hCD27.15 (See WO 2012 / 004367. incorporated herein by reference in its entirety), and boserolimab (See entry 1308 in the imgt.org / mAb-DB database). In some embodiments, the CD27 scFv comprises, from N-terminus to C-terminus, VH domain - linker - VL domain. In some embodiments, the scFv comprises, from N-terminus to C-terminus, VL domain - linker -VH domain.

[0126] In some embodiments, the targeting moiety comprises an scFv that binds to CD4 (“a CD4 scFv’'). In some embodiments, the CD4 scFv is based on the ibalizumab antibody. In some embodiments, the CD4 scFv comprises, from N-terminus to C-terminus, VH domain - linker -VL domain. In some embodiments, the scFv comprises, from N-terminus to C-terminus, VL domain - linker - VH domain.

[0127] In some embodiments, the targeting moiety comprises an scFv that binds to CD28 (“a CD28 scFv”). In some embodiments, the CD28 scFv comprises, from N-terminus to C-terminus, VH domain - linker - VL domain. In some embodiments, the scFv comprises, from N-terminus to C-terminus, VL domain - linker - VH domain.

[0128] In some embodiments, the targeting moiety comprises an scFv that binds to aTCR (‘“a TCR scFv”). In some embodiments, the TCR scFv is based on an antibody selected from BMA031, GL1BM, GL1BM VH28, GL1BM VH31, HEBE, HEBE H10, and HEBE H66 described in WO 2013 / 037484, incorporated herein by reference in its entirety'. In some34IPTS / 200318117.8Attorney Docket No.: AZL-004WOembodiments, the TCR scFv comprises, from N-terminus to C-terminus, VH domain - linker - VL domain. In some embodiments, the scFv comprises, from N-terminus to C-terminus, VL domain - linker - VH domain.

[0129] Exemplary scFv sequences are provided below in Table 1. Linker sequences are indicated in bold and italicized text.Table 1: Exemplary scFv sequencesT arget Clone name scFv scFv sequence (AA) SEQ ID:Ref.CD3 UCHT1 7a.1 EVQLQQSGPELVKPGASMKISCKASGYSFTGYT 3 MNWVKQSHGKNLEWMGLINPYKGVSTYNQKF KDK ATLTVDKS S ST AYMELLSLTSEDS AVYYC A RSGYYGDSDWYFDVWGQGTTLTVFGGGGS'G'G' GG5GGGGADIQMTQTTSSLSASLGDRVTISCRAS QDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVP SKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTL PWTFAGGTKLEIKS CD3 UCHT1 7a.2 DIQMTQTTSSLSASLGDRVTISCRASQDIRNYLN 4 WYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGS GTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGG TKLEIKGGGGYGGGGAGGGGYEVQLQQSGPELV KPGASMKISCKASGYSFTGYTMNWVKQSHGKN LE WMGLINPYKGVSTYNQKFKDKATLTVDKS S S TAYMELLSLTSEDSAVYYCARSGYYGDSDWYF DVWGQGTTLTVFS CD3 OKT3 7b MQVQLLESGAELARPGASVKMSCKASGYTFTR 5 YTMHWVKQRPGQGLEWIGYINPSRGYTNYNQK FKDKATLTTDKS S STAYMQLS SLTSEDS AVYYC AGYYDDHYCLDYWGQGTLVTVSSGGG'GS'G'G'G' GYGGGGAD1VMTQSPAIMSASPGEKVTMTCSASS SVSYMNWYQQKSGTSPKRWIYDTSKLASGVPA HFRGSGSGTSYSLTISGMEAEDAATYYCQQWSS NPFTFGSGTKLEIKRS CD3 Acapatamab 7f.1 EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYA 6 MNWVRQAPGKGLEWVARIRSKYNNYATYYAD SVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYY C VRHGNFGNSYISYW AYWGQGTLVTVS S GGGG YGGGGAGGGG’AQTVVTQEPSLTVSPGGTVTLTC GSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKF LAPGTPARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLS CD3 Acapatamab 7f.2 QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNY 7 PNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGS LLGGKAALTLSGVQPEDEAEYYCVLWYSNRWV FGGGTKLTVLG'G'GGA'G’G’G’GA'GGGGVEVQLVES GGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQ APGKGLEWVARIRSKYNNYATYYADSVKDRFTI SRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSS35IPTS / 200318117.8Attorney Docket No.: AZL-004WOTarget Clone name scFv scFv sequence (AA) SEQ ID:Ref.CD3 N / A 7g DIQMTQSPSSLSASVGDRVTITCRASQDIRNYLN 8 WYQQKPGKAPKLLIYYTSRLESGVPSRFSGSGSG TDYTLTISSLQPEDFATYYCQQGNTLPWTFGQGT KVEIKGGGG5GGGG5GGGGSEVQLVESGGGLV QPGGSLRLSCAASGYSFTGYTMNWVRQAPGKG LEWVALINPTKGVSTYNQKFKDRFTISVDKSKN TAYLQMNSLRAEDTAVYYCARSGYYGDSDWYF DVWGQGTLVTVSSS CD3 0KT3 7h.l QVQLQQSGAELARPGASVKMSCKASGYTFTRY 9 TMHWVKQRPGQGLEWIGYINPSRGYTNYNQKF KDKATLTTDKSSSTAYMQLSSLTSEDSAVYYCA RYYDDHYCLDYWGQGTTLTVS S GGGGSGGGGS GGGGYQIVETQSPAIMSASPGEKVTMTCSASSSV SYMNWYQQKSGTSPKRWIYDTSKLASGVPAHF RGSGSGTSYSLTISGMEAEDAATYYCQQWSSNP FTFGSGTKLEINS CD3 0KT3 7h.2 QIVLTQSPAIMSASPGEKVTMTCSASSSVSYMN 10 WYQQKSGTSPKRWIYDTSKLASGVPAHFRGSGS GTSYSLTISGMEAEDAATYYCQQWSSNPFTFGS GTKLEINGGGGYGGGG5GGGG5QVQLQQSGAEL ARPGASVKMSCKASGYTFTRYTMHWVKQRPGQ GLEWIGYINPSRGYTNYNQKFKDKATLTTDKSS STAYMQLSSLTSEDSAVYYCARYYDDHYCLDY WGQGTTLTVSSS CD3 hOKT3 7i.1 QVQLVQSGGGVVQPGRSLRLSCKASGYTFTRYT 11 MHWVRQAPGKGLEWIGYINPSRGYTNYNQKVK DRFTISRDNSKNTAFLQMDSLRPEDTGVYFCAR YYDDHYCLDYWGQGTPVTVSSGGGG'YG'G'G'G'YG' GGGSDIQMTQSP S SLS AS VGDRVTITC S ASS S VSY MNWYQQTPGKAPKRWIYDTSKLASGVPSRFSGS GSGTDYTFTISSLQPEDIATYYCQQWSSNPFTFG QGTKLQITS CD3 hOKT3 7i.2 DIQMTQSPSSLSASVGDRVTITCSASSSVSYMNW 12 YQQTPGKAPKRWIYDTSKLASGVPSRFSGSGSG TDYTFTIS SLQPEDI ATYYCQQ WS SNPFTFGQGT KLQITGG'GGYG'G'G'G'YG'GGG’YQVQLVQSGGGVV QPGRSLRLSCKASGYTFTRYTMHWVRQAPGKG LEWIGYINPSRGYTNYNQKVKDRFTISRDNSKNT AFLQMDSLRPEDTGVYFCARYYDDHYCLDYWG QGTPVTVSSS CD3 FN-18 7J.1 QVQLQQSEAELARPGASVKMSCKASGYTFTDYT 13 IHWLKQRPGQGLDWIGYFNPSSESTEYNRKFKD RTILTADRSSTTAYMQLSSLTSEDSAVYYCSRKG EKLLGNRYWYFDVWGAGTSVTVSS GGGGSGGG GYGGGGSDIVMSQSPSSLAVSVGEKVTMSCKSS QSLLYSSNQKNYLAWYQQKPGQSPKLLINWAST RESGVPDRFTGSGSRTDFTLTISSVKAEDLAVYF CQQFYSYPPTFGGGTKLEIKS CD3 FN-18 7J.2 DIVMSQSPSSLAVSVGEKVTMSCKSSQSLLYSSN 14QKNYLAWYQQKPGQSPKLLINWASTRESGVPD36IPTS / 200318117.8Attorney Docket No.: AZL-004WOTarget Clone name scFv scFv sequence (AA) SEQ ID:Ref.RFTGSGSRTDFTLTISSVKAEDLAVYFCQQFYSY PPTFGGGTKLEIKGGGGAGGGGAGGGGAQVQLQ QSEAELARPGASVKMSCKASGYTFTDYTIHWLK QRPGQGLDWIGYFNPS SESTEYNRKFKDRTILTA DRSSTTAYMQLSSLTSEDSAVYYCSRKGEKLLG NRYWYFDVWGAGTS VTVS S S CD3 SP34-2 7k.1 EVKLLESGGGLVQPKGSLKLSCAASGFTFNTYA 15 MNWVRQAPGKGLEWVARIRSKYNNYATYYAD SVKDRFTISRDDSQSILYLQMNNLKTEDTAMYY CVRHGNFGNSYVSWFAYWGQGTLVTVSAGGG GSGGGGSGGGGS'QAVVTQESALTTSPGETVTLT CRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTN KRAPGVPARFSGSLIGDKAALTITGAQTEDEAIY FCALWYSNLWVFGGGTKLTVLS CD3 SP34-2 7k.2 QAVVTQESALTTSPGETVTLTCRSSTGAVTTSNY 16 ANWVQEKPDHLFTGLIGGTNKRAPGVPARFSGS LIGDKAALTITGAQTEDEAIYFCALWYSNLWVF GGGTKLTVL GGGGSGGGGSGGGGSEVKLLES G GGLVQPKGSLKLSCAASGFTFNTYAMNWVRQA PGKGLEWVARIRSKYNNYATYYADSVKDRFTIS RDDSQSILYLQMNNLKTEDTAMYYCVRHGNFG NSYVSWFAYWGQGTLVTVSAS CD4 ibalizumab 9a.1 QVQLQQSGPEVVKPGASVKMSCKASGYTFTSY 17 VIHWVRQKPGQGLDWIGYINPYNDGTDYDEKF KGKATLTSDTSTSTAYMELSSLRSEDTAVYYCA REKDNYATGAWF AYWGQGTLVTVS S GGGGSG GGGSGGGGSADIVMTQSPDSLAVSLGERVTMNC KSSQSLLYSTNQKNYLAWYQQKPGQSPKLLIYW ASTRESGVPDRFS GS GSGTDFTLTIS S V QAEDV A VYYC QQYYSYRTFGGGTKLEIKS CD4 ibalizumab 9a.2 DIVMTQSPDSLAVSLGERVTMNCKSSQSLLYST 18 NQKNYLAWYQQKPGQSPKLLIYWASTRESGVP DRFSGSGSGTDFTLTISSVQAEDVAVYYCQQYY SYRTFGGGTKLEIKSGGGGAGGGGAGGGGAAQV QLQQSGPEVVKPGASVKMSCKASGYTFTSYVIH WVRQKPGQGLDWIGYINPYNDGTDYDEKFKGK ATLTSDTSTSTAYMELSSLRSEDTAVYYCAREK DNYATGAWF AYWGQGTLVTV S S CD28 N / A 15a QVQLVQSGAEVKKPGASVKVSCKASGYTFTSY 19 GISWVRQAPGQGLEWMGWISAYNDNTHYAQK LQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYC ATQAAMDVWGQGTLVTVSS GGGGSGGGGSGG GGASYELTQPPSASGTPGQRVTISCSGSRSNIGGN TVNWYQQLPGTAPKLLIYANDQRPSGVPDRVSG SKSGTSASLAISGLQSEDEAHYYCAAWDDRLNG VVFGGGTKLTVLS CD28 N / A 15b.l QVQLQQSGPELVKPGTSVRISCEASGYTFTSYYI 20 HWVKQRPGQGLEWIGCIYPGNVNTNYNEKFKD KATLIVDTSSNTAYMQLSRMTSEDSAVYFCTRSHYGLDWNFDVWGAGTTVTVSSGGGGAGGGGA37IPTS / 200318117.8Attorney Docket No.: AZL-004WOTarget Clone name scFv scFv sequence (AA) SEQ ID:Ref.GGGG5SDIQMNQSPSSLSASLGDTITITCHASQNI YVWLNWYQQKPGNIPKLLIYKASNLHTGVPSRF SGSGSGTGFTLTISSLQPEDIATYYCQQGQTYPYT FGGGTKLEIKS CD28 N / A 15b.2 DIQMNQSPSSLSASLGDTITITCHASQNIYVWLN 21 WYQQKPGNIPKLLIYKASNLHTGVPSRFSGSGSG TGFTLTISSLQPEDIATYYCQQGQTYPYTFGGGT KLEIKGGGGYGGGGYGGGGSSQVQLQQSGPELV KPGTSVRISCEASGYTFTSYYIHWVKQRPGQGLE W IGC I Y PGNVNTNYNEKFKDKATLIVDTS SNTA YMQLSRMTSEDSAVYFCTRSHYGLDWNFDVW GAGTTVTVSSS CD28 N / A 15c.1 VQLQQSGAELKKPGASVKVSCKASGYTFTEYIIH 22 WIKLRSGQGLEWIGWFYPGSNDIQYNAQFKGKA TLTADKSSSTVYMRRDDFSGYDALPYWGQGTL VTVSAG'G'G'G'YGGGG’YG'G'G'G'YSDIQMTQSPSSLS ASVGDRVTITCKTNENIYSNLAWYQQKDGKSPQ LLIYAATHLVEGVPSRFSGSGSGTQYSLTISSLQP EDFGNYYCQHFWGTPATFGGGTKLEIKS CD28 N / A 15c.2 DIQMTQSPSSLSASVGDRVTITCKTNENIYSNLA 23 WYQQKDGKSPQLLIYAATHLVEGVPSRFSGSGS GTQYSLTISSLQPEDFGNYYCQHFWGTPATFGG GTKLEIKGGGG5GGGGYGGGG5SVQLQQSGAEL KKPGASVKVSCKASGYTFTEYIIHWIKLRSGQGL EWIGWFYPGSNDIQYNAQFKGKATLTADKSSST VYMRRDDFSGYDALPYWGQGTLVTVSAS CD5 N / A 50a.1 NIQLVQSGPELKKPGETVKISCKASGYTFTNYGM 24 NWVKQAPGKGLRWMGWINTHTGEPTYADDFK GRFAFSLETSASTAYLQINNLKNEDTATYFCTRR GYDWYFDVWGAGTTVTVSS GGGGSGGGGSGG GGYSDIKMTQSPSSMYASLGERVTITCKASQDIN SYLSWFHHKPGKSPKTLIYRANRLVDGVPSRFSG SGSGQDYSLTISSLDYEDMGIYYCQQYDESPWTF GGGTKLEMKS CD5 N / A 50a.2 DIKMTQSPSSMYASLGERVTITCKASQDINSYLS 25 WFHHKPGKSPKTLIYRANRLVDGVPSRFSGSGS GQDYSLTISSLDYEDMGIYYCQQYDESPWTFGG GTKLEMKGG'G'G'YGGGG’YG'G'G'G'YSNIQLVQSGPE LKKPGETVKISCKASGYTFTNYGMNWVKQAPG KGLRWMGWINTHTGEPTYADDFKGRFAFSLETS ASTAYLQINNLKNEDTATYFCTRRGYDWYFDV WGAGTTVTVSSS CD5 HOLO 50b.1 QVTLKESGPGILKPSQTLSLTCSFSGFSLSTSGMG 26 VGWIRQPSGKGLEWLAHIWWDDDVYYNPSLKN QLTISKDASRDQVFLKITNLDTADTATYYCVRRR ATGTGFDYWGQGTTLTV S S GGGGSGGGGSGGG GYSNIVMTQSHKFMSTSVGDRVSIACKASQDVG TAVAWYQQKPGQSPKLLIYWTSTRHTGVPDRFT GSGSGTDFTLTITNVQSEDLADYFCHQYNSYNTFGSGTRLELKS38IPTS / 200318117.8Attorney Docket No.: AZL-004WOTarget Clone name scFv scFv sequence (AA) SEQ ID:Ref.CD5 HOLO 50b.2 NIVMTQSHKFMSTSVGDRVSIACKASQDVGTAV 27 AWYQQKPGQSPKLLIYWTSTRHTGVPDRFTGSG SGTDFTLTITNVQSEDLADYFCHQYNSYNTFGSG TRLELKGGGGSGGGGSGGGGSSQVTLKESGPGI LKPSQTLSLTCSFSGFSLSTSGMGVGWIRQPSGK GLEWLAHIWWDDDVYYNPSLKNQLTISKDASR DQVFLKITNLDTADTATYYCVRRRATGTGFDY WGQGTTLTVSSS CD5 HILI 50c.1 EVQLVESGGGVVQPGRSLRLSCTFSGFSLSTSGM 28 GVGWIRQAPGKGLEWVAHIWWDDDVYYNPSL KSRLT1TKDASTDTVYMELSSLRSEDTAVYYCV RRRATGTGFDYWGQGTLVTVSS GGGGSGGGGS GGGGSSN1VMTQSPSSLSASVGDRVTITCQASQD VGTAVAWYQQKPDQSPKLLIYWTSTRHTGVPD RFTGSGSGTDFTLTISSLQPEDIATYFCHQYNSYN TFGSGTKLEIKS CD5 HILI 50c.2 NIVMTQSPSSLSASVGDRVTITCQASQDVGTAVA 29 WYQQKPDQSPKLLIYWTSTRHTGVPDRFTGSGS GTDFTLTISSLQPEDIATYFCHQYNSYNTFGSGTK LEIKGGGGAGGGGAGGGGASEVQLVESGGGVVQ PGRSLRLSCTFSGFSLSTSGMGVGWIRQAPGKGL EWV AHIWWDDDVYYNP SLKSRLTITKD ASTDT VYMELSSLRSEDTAVYYCVRRRATGTGFDYWG QGTLVTVSSS CD5 H1L3 50d.l EVQLVESGGGVVQPGRSLRLSCTFSGFSLSTSGM 30 GVGWIRQAPGKGLEWVAHIWWDDDVYYNPSL KSRLTITKDASTDTVYMELSSLRSEDTAVYYCV RRRATGTGFDYWGQGTLVTVSS GGGGSGGGGS GGGGASNIVMTQSPAFLSVTPGEKVTITCQASQD VGTAVAWYQQKPDQSPKLLIYWTSTRHTGVPD RFTGSGSGTDFTFTISSLEAEDAATYFCHQYNSY NTFGSGTKLEIKS CD5 H1L3 50d.2 NIVMTQSPAFLSVTPGEKVTITCQASQDVGTAVA 31 WYQQKPDQSPKLLIYWTSTRHTGVPDRFTGSGS GTDFTFTISSLEAEDAATYFCHQYNSYNTFGSGT KLEIKGGGGAGGGGAGGGGS'SEVQLVESGGGVV QPGRSLRLSCTFSGFSLSTSGMGVGWIRQAPGKG LEWVAHIWWDDDVYYNPSLKSRLTITKDASTDT VYMELSSLRSEDTAVYYCVRRRATGTGFDYWG QGTLVTVSSS CD5 H2L2 50e.l QVTLKESGPALVKPTQTLTLTCTFSGFSLSTSGM 32 GVGWIRQPPGKGLEWVAHIWWDDDVYYNPSL KSRLTITKDASKDQVVLTMTNMDPVDTATYYC VRRRATGTGFDYWGQGTLVTVS S GGGGSGGGG AGGGGASNIVMTQSPPTLSLSPGERATLSCRASQ DVGTAVAWYQQKPDQSPKLLIYWTSTRHTGVP DRFTGSGSGTDFTLTISRLEPEDFAVYFCHQYNS YNTFGSGTKLEIKS CD5 H2L2 50e.2 NIVMTQSPPTLSLSPGERATLSCRASQDVGTAVA 33WYQQKPDQSPKLLIYWTSTRHTGVPDRFTGSGS39IPTS / 200318117.8Attorney Docket No.: AZL-004WOTarget Clone name scFv scFv sequence (AA) SEQ ID:Ref.GTDFTLTISRLEPEDFAVYFCHQYNSYNTFGSGT KLEIKGGGGAGGGGAGGGGSSQVTLKESGPALV KPTQTLTLTCTFSGFSLSTSGMGVGWIRQPPGKG LEWVAHIWWDDDVYYNPSLKSRLTITKDASKD QVVLTMTNMDPVDTATYYCVRRRATGTGFDY WGQGTLVTVSSS CD5 H3L1 50f.l QVTLKESGPVLVKPTETLTLTCTFSGFSLSTSGM 34 GVGWIRQAPGKGLEWVAHIWWDDDVYYNPSL KSRLTITKDASKDQVSLKLSSVTAADTAVYYCV RRRATGTGFDYWGQGTLVTVSS GGGGSGGGGS GGGGSSNIVMTQSPSSLSASVGDRVTITCQASQD VGTAVAWYQQKPDQSPKLLIYWTSTRHTGVPD RFTGSGSGTDFTLTISSLQPEDIATYFCHQYNSYN TFGSGTKLEIKS CD5 H3L1 50f.2 N1VMTQSPSSLSASVGDRVTITCQASQDVGTAVA 35 WYQQKPDQSPKLLIYWTSTRHTGVPDRFTGSGS GTDFTLTISSLQPEDIATYFCHQYNSYNTFGSGTK LEIKGGGGAGGGG5GGGGASQVTLKESGPVLVK PTETLTLTCTFSGFSLSTSGMGVGWIRQAPGKGL EWV AHIWWDDDVYYNP SLKSRLTITKD ASKDQ VSLKLSSVTAADTAVYYCVRRRATGTGFDYWG QGTLVTVSSS CD5 H3L3 50g.1 QVTLKESGPVLVKPTETLTLTCTFSGFSLSTSGM 36 GVGWIRQAPGKGLEWVAHIWWDDDVYYNPSL KSRLTITKDASKDQVSLKLSSVTAADTAVYYCV RRRATGTGFDYWGQGTLVTVSS GGGGSGGGGS GGGGASNIVMTQSPAFLSVTPGEKVTITCQASQD VGTAVAWYQQKPDQSPKLLIYWTSTRHTGVPD RFTGSGSGTDFTFTISSLEAEDAATYFCHQYNSY NTFGSGTKLEIKS CD5 H3L3 50g.2 NIVMTQSPAFLSVTPGEKVTITCQASQDVGTAVA 37 WYQQKPDQSPKLLIYWTSTRHTGVPDRFTGSGS GTDFTFTISSLEAEDAATYFCHQYNSYNTFGSGT KLEIKGGGGAGGGGAGGGGASQVTLKESGPVLV KPTETLTLTCTFSGFSLSTSGMGVGWIRQAPGKG LEWVAHIWWDDDVYYNPSLKSRLTITKDASKD QVSLKLSSVTAADTAVYYCVRRRATGTGFDYW GQGTLVTVSSS CD7 N / A 51.a.l EVQLVESGGGLVKPGGSLKLSCAASGLTFSSYA 38 MSWVRQTPEKRLEWVASISSGGFTYYPDSVKGR FTISRDNARNILYLQMSSLRSEDTAMYYCARDE VRGYLDVWGAGTTVTVSS GGGGSGGGGSGGG GASDIQMTQTTSSLSASLGDRVTISCSASQGISNY LNWYQQKPDGTVKLLIYYTSSLHSGVPSRFSGS GSGTDYSLTISNLEPEDIATYYCQQYSKLPYTFG GGTKLEIKS CD7 N / A 51a.2 DIQMTQTTSSLSASLGDRVTISCSASQGISNYLN 39 WYQQKPDGTVKLLIYYTSSLHSGVPSRFSGSGSG TDYSLTISNLEPEDIATYYCQQYSKLPYTFGGGTKLEIKGGGG5GGGGAGGGGASEVQLVESGGGLV40IPTS / 200318117.8Attorney Docket No.: AZL-004WOTarget Clone name scFv scFv sequence (AA) SEQ ID:Ref.KPGGSLKLSCAASGLTFSSYAMSWVRQTPEKRL EWVASISSGGFTYYPDSVKGRFTISRDNARNILY LQMSSLRSEDTAMYYCARDEVRGYLDVWGAG TTVTVSSS CD7 grisnilimab 51b.l QIQLVQSGPELKKPGETVKISCKASGYTFTNYGM 40 NWVKQAPGKGLMWLGWINTYTGEPTYADDFK GRFAFSLETSASTAYLQINNLKNEDTATYFCAR WAYFYGS SPYFFDYWGQGTTLTVS S GGGGSGG GGAGG'GG'ASQAVVTQESALTTSPGETVTLTCRSS TGAVTTSNYANWVQEKPDHLFTGLIGGTNNRAP GVPARFSGSL1GDKAALT1TGAQTEDEA1YFCAL WCSNHLVFGGGTKLTVLS CD7 grisnilimab 51b.2 QAVVTQESALTTSPGETVTLTCRSSTGAVTTSNY 41 ANWVQEKPDHLFTGLIGGTNNRAPGVPARFSGSL1GDKAALTITGAQTEDEA1YFCALWCSNHLVFG GGTKLTVLGGGGAGGGGAGGGGASQIQLVQSGP ELKKPGETVKISCKASGYTFTNYGMNWVKQAP GKGLMWLGWINTYTGEPTYADDFKGRFAFSLE TSASTAYLQINNLKNEDTATYFCARWAYFYGSS PYFFDYWGQGTTLTVS SS CD27 M2177 52a.1 QVQLQQSGPELVKPGASVK1SCKASGYAFSSSW 42 MNWVKQRPGKGLEWIGRIYPGDGDTNYNGKFK GKATLTADKSSSTAYMQLSSLTSEDSAVYFCAR SDYYGDYGFAYWGQGTLVTVSAGGGGAGGGG AGGGGASDIVLTQSPASLAVSLGQRATISCKASQ SVDYAGDSYMNWYQQKPGQPPKLLIYAASNLE SGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQ QSNEDPYTFGGGTKLEIKS CD27 M2177 52a.2 DIVLTQSPASLAVSLGQRATISCKASQSVDYAGD 43 SYMNWYQQKPGQPPKLLIYAASNLESGIPARFS GSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPYT FGGGTKLEIKGGGGVGGGGAGGGGASQVQLQQS GPELVKPGASVKISCKASGYAFSSSWMNWVKQ RPGKGLEWIGRIYPGDGDTNYNGKFKGKATLTA DKSSSTAYMQLSSLTSEDSAVYFCARSDYYGDY GFAYWGQGTLVTVSAS CD27 H2191 52b.1 QVQLVESGGGLVKPGGSLRLSCAASGFTFSSYG 44 MSWIRQAPGKGLEWVSYIDEGGGQTIYPDSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYCARH RGNPFDYWGQGTLVTVS S GGGGSGGGGSGGGG ASDIQMTQSPSSLSASVGDRVTITCRASKSVSEGR WSFMHWYQQKPGKAPKLLIYVASRLESGVPSRF SGSGSGTDFTFTISSLQPEDIATYYCQHSRELPWT FGQGTKVEIKS CD27 H2191 52b.2 DIQMTQSPSSLSASVGDRVTITCRASKSVSEGRW 45 SFMHWYQQKPGKAPKLLIYVASRLESGVPSRFS GSGSGTDFTFTISSLQPEDIATYYCQHSRELPWTF GQGTKVEIKGGGGAGGGGAGGGGASQVQLVES GGGLVKPGGSLRLSCAASGFTFSSYGMSWIRQAPGKGLEWVSYIDEGGGQTIYPDSVKGRFTISRDN41IPTS / 200318117.8Attorney Docket No.: AZL-004WOTarget Clone name scFv scFv sequence (AA) SEQ ID:Ref.AKNSLYLQMNSLRAEDTAVYYCARHRGNPFDY WGQGTLVTVSSS CD27 M2191 52c.1 EVKLVESGGGLVKPGGSLKLSCAASGFTFSSYT 46 MSWVRQTPEKRLEWVAYISSGGGNTYYPDSVK GRFTISRDNARNTLYLQMS SLRSEDT AMYYC SR HRGNPFDYWGQGTTLTVS S GGGGSGGGGSGGG GVSDIVLTQSPASLAVSLGQRATISCRASKSVSTS GYSFMHWYQQKPGQPPKLLIYLASNLESGVPAR FSGSGSGTDFTLNIHPVEEEDAATYYCQHSRELP WTFGGGTKLEIKS CD27 M2191 52c.2 DIVLTQSPASLAVSLGQRATISCRASKSVSTSGYS 47 FMHWYQQKPGQPPKLLIYLASNLESGVPARFSG SGSGTDFTLNIHPVEEEDAATYYCQHSRELPWTF GGGTKLEIKGGGGVGGGGVGGGGVSEVKLVESG GGLVKPGGSLKLSCAASGFTFSSYTMSWVRQTP EKRLEWV AYIS S GGGNTYYPDS VKGRFTISRDN ARNTLYLQMSSLRSEDTAMYYCSRHRGNPFDY WGQGTTLTVSSS CD27 varlilumab 52d.l QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYD 48 MHWVRQAPGKGLEWVAVIWYDGSNKYYADSV KGRFTISRDNSKNTLYLQMNSLRAEDCHDTAVY YC ARGSGNWGFFDYWGQGTLVTVSS GGGGSGG GGVGGGGASDIQMTQSPSSLSASVGDRVTITCRA SQGISRWLAWYQQKPEKAPKSLIYAASSLQSGV PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQCKA PPADYNTYPRTFGQGTKVEIKS CD27 varlilumab 52d.2 DIQMTQSPSSLSASVGDRVTITCRASQGISRWLA 49 WYQQKPEKAPKSLIYAASSLQSGVPSRFSGSGSG TDFTLTIS SLQPEDFATYYCQQCKAPP ADYNTYP RTFGQGTKVEIKGGGGVGGGGVGGGGVSQVQLV ESGGGVVQPGRSLRLSCAASGFTFSSYDMHWVR QAPGKGLEWVAVIWYDGSNKYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDCHDTAVYYCARG SGNWGFFDYWGQGTLVTVSSS CD27 3C2 52e.l QAQLQESGPGLVKPSETLSLTCTVSTGSISGYYW 50 SWIRQPPGKGLEWIGYNYYSGSTNYNPSLKSRV TISIDTSKNQFSLKLNSVTAADTAVYYCARYPLI RGAFDYWGQGTLVTVSSGGGGVGGGGVGGGGV SDIVMTQSPLSLPVTPGEPASISCRSSQNLLHTNG YNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCMQALQTP LTFGGGTKVEIKS CD27 3C2 52e.2 DIVMTQSPLSLPVTPGEPASISCRSSQNLLHTNGY 51 NYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFS GSGSGTDFTLKISRVEAEDVGVYYCMQALQTPL TFGGGTKVEIKGGGGVGGGGAGGGGVSQAQLQE SGPGLVKPSETLSLTCTVSTGSISGYYWSWIRQPP GKGLEWIGYNYYSGSTNYNPSLKSRVTISIDTSK NQFSLKLNSVTAADTAVYYCARYPLIRGAFDYWGQGTLVTVSSS42IPTS / 200318117.8Attorney Docket No.: AZL-004WOTarget Clone name scFv scFv sequence (AA) SEQ ID:Ref.CD27 2B3 52f.l QVQLVQSGAEVKKPGASVKVSCKASGYTFTGY 52 YIHWVRQAPGQGLEWMGWINPNSGGTNSAQKF QDRVTITRVTSINTAYMELSRLRSDDTAVYFCAR DRLVLPWFGEIFPD AFDIWGQGTLVTVS S GGGG AGGGGAGGGGASEIVMTQSPATLSVSPGERATLS CRASQSIRSNLAWYQQKPGQAPRLLIYGASTRA TGIPARFSGSGSGTEFTLTISSLQSENFAVYYCQQ YNNWPLTFGGGTKVEIKS CD27 2B3 52f.2 EIVMTQSPATLSVSPGERATLSCRASQSIRSNLA 53 WYQQKPGQAPRLLIYGASTRATGIPARFSGSGSG TEFTLTISSLQSENFAVYYCQQYNNWPLTFGGGT EIKGGGGSGGGGSGGGGSSQVQLQQSGAEVK KKPGASVKVSCKASGYTFTGYY1HWVRQAPGQ GLEWMGWINPNSGGTNSAQKFQDRVTITRVTSI NTAYMELSRLRSDDTAVYFCARDRLVLPWFGEI FPDAFDIWGQGTLVTVSSS CD27 hCD27.15 52g.1 EVRLQQSGADLVKPGASVKLSCTASGFIIKATY 54 MHWVRQRPEQGLEWIGRIDPANGETKYDPKFQ VKATITADTSSSTAYLQLNSLTSDDTAVYYCAR YAWYFDVWGAGTTVTVSS GGGGSGGGGSGGG GASDIQMTQSPASLSASVGDTVTITCRASENIYSF LAWYHQKQGRSPQLLVYHAKTLAEGVPSRFSGS GSGTQFSLKINSLQAEDFGSYYCQHYYGSPLTFG AGTKLEVKS CD27 hCD27.15 52g.2 DIQMTQSPASLSASVGDTVTITCRASENIYSFLA 55 WYHQKQGRSPQLLVYHAKTLAEGVPSRFSGSGS GTQFSLKINSLQAEDFGSYYCQHYYGSPLTFGAG TKLEVKGGGGAGGGGAGGGGASEVRLQQSGAD LVKPGASVKLSCTASGFIIKATYMHWVRQRPEQ GLEWIGRIDP ANGETKYDPKFQVKATITADTS S S TAYLQLNSLTSDDTAVYYCARYAWYFDVWGA GTTVTVSSS CD27 boserolimab 52h.1 EIQLVQSGAEVKKPGASVKVSCKASGYTFTNYG 56 MNWVKQAPGQGLKWMGWINTNTGEPTYAEEF KGRFTFTLDTSISTAYMELSSLRSEDTAVYYCAR EGDAMDYWGQGTTVTVSS GGGGSGGGGSGGG GASEIVLTQSPATLSLSPGERATLSCSASSSVSYM HWYQQKPGQAPKRWIYDTSKLASGVPARFSGS GSGTDYSLTISSLEPEDFAVYYCQQWNSYPFTFG QGTKLEIKS CD27 boserolimab 52h.2 EIVLTQSPATLSLSPGERATLSCSASSSVSYMHW 57 YQQKPGQAPKRWIYDTSKLASGVPARFSGSGSG TDYSLTISSLEPEDFAVYYCQQWNSYPFTFGQGT KLEIKGGGGAGGGGAGGGGSSEIQLVQSGAEVK KPGASVKVSCKASGYTFTNYGMNWVKQAPGQ GLKWMGWINTNTGEPTYAEEFKGRFTFTLDTSIS TAYMELS SLRSEDTAVYYC AREGD AMDYWGQ GTTVTVSSS TCR BMA031 53a.1 EVQLQQSGPELVKPGASVKMSCKASGYKFTSYV 58MHWVKQKPGQGLEWIGYINPYNDVTKYNEKFK43IPTS / 200318117.8Attorney Docket No.: AZL-004WOTarget Clone name scFv scFv sequence (AA) SEQ ID:Ref.GKATLTSDKSSSTAYMELSSLTSEDSAVHYCAR GSYYDYDGFVYWGQGTLVTVSAGGGGSGGGG AGGGGASQIVLTQSPAIMSASPGEKVTMTCSATS SVSYMHWYQQKSGTSPKRWIYDTSKLASGVPA RFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSN PLTFGAGTKLELKS TCR BMA031 53a.2 QIVLTQSPAIMSASPGEKVTMTCSATSSVSYMH 59 WYQQKSGTSPKRWIYDTSKLASGVPARFSGSGS GTSYSLTISSMEAEDAATYYCQQWSSNPLTFGA GTKLELKGGGGAGGGGAGGGGSSEVQLQQSGPE LVKPGASVKMSCKASGYKFTSYVMHWVKQKP GQGLEWIGYINPYNDVTKYNEKFKGKATLTSDK SSSTAYMELSSLTSEDSAVHYCARGSYYDYDGF VYWGQGTLVTVSAS TCR GL1BM 53b.l QVQLVQSGAEVKKPGASVKVSCKASGYKFTSY 60 VMHWVRQAPGQRLEWMGYINPYNDVTKYNEK FKGKATITRDTS ANTAYMELS SLRSEDTAVYYC ARGSYYDYDGFVYWGQGTLVTVSS GGGGSGGG GAGGGGASEIVLTQSPATLSLSPGERATLSCSATS SVSYMHWYQQKPGQAPRRWIYDTSKLASGVPA RFSGSGSGTDFTLTISSLEPEDFAVYYCQQWSSN PLTFGGGTKVEIKS TCR GL1BM 53b.2 EIVLTQSPATLSLSPGERATLSCSATSSVSYMHW 61 YQQKPGQAPRRWIYDTSKLASGVPARFSGSGSG TDFTLTIS SLEPEDFAVYYCQQWS SNPLTFGGGT KVEIKGGGGSGGGGAGGGGSSQVQLVQSGAEV KKPGASVKVSCKASGYKFTSYVMHWVRQAPGQ RLEWMGYINPYNDVTKYNEKFKGKATITRDTSA NTAYMELSSLRSEDTAVYYCARGSYYDYDGFV YWGQGTLVTVSSS TCR GL1BM 53c.1 QVQLVQSGAEVKKPGASVKVSCKASGYKFTSY 62 VH28 VMHWVKQAPGQGLEWIGYINPYNDVTKYNEKF KGRVTITRDTSASTAYMELSSLRSEDTAVYYCA RGSYYDYDGFVYWGQGTLVTVS S GGGGSGGGG SGGGGSSEIVLTQSPATLSLSPGERATLSCSATSS VSYMHWYQQKPGQAPRRWIYDTSKLASGVPAR FSGSGSGTDFTLTISSLEPEDFAVYYCQQWSSNP LTFGGGTKVEIKS TCR GL1BM 53c.2 EIVLTQSPATLSLSPGERATLSCSATSSVSYMHW 63 VH28 YQQKPGQAPRRWIYDTSKLASGVPARFSGSGSG TDFTLTIS SLEPEDFAVYYCQQWS SNPLTFGGGT KVEIKGGGGAGGGGAGGGGASQVQLVQSGAEV KKPGASVKVSCKASGYKFTSYVMHWVKQAPG QGLEWIGYINPYNDVTKYNEKFKGRVTITRDTS ASTAYMELSSLRSEDTAVYYCARGSYYDYDGF VYWGQGTLVTVSSS TCR GL1BM 53d.l QVQLVQSGAEVKKPGASVKVSCKASGYKFTSY 64 VH31 VMHWVRQAPGQGLEWIGYINPYNDVTKYNEKFKGRVTITRDTSASTAYMELSSLRSEDTAVYYCARGSYYDYDGFVYWGQGTLVTVS S GGGGSGGGG44IPTS / 200318117.8Attorney Docket No.: AZL-004WOTarget Clone name scFv scFv sequence (AA) SEQ ID:Ref.SGGGGVSEIVLTQSPATLSLSPGERATLSCSATSS VSYMHWYQQKPGQAPRRWIYDTSKLASGVPAR FSGSGSGTDFTLTISSLEPEDFAVYYCQQWSSNP LTFGGGTKVEIKS TCR GL1BM 53d.2 EIVLTQSPATLSLSPGERATLSCSATSSVSYMHW 65 VH31 YQQKPGQAPRRWIYDTSKLASGVPARFSGSGSG TDFTLTIS SLEPEDFAVYYCQQ WS SNPLTFGGGT KVEIKGGGGSGGGGSGGGGSSQVQLVQSGAEV KKPGASVKVSCKASGYKFTSYVMHWVRQAPGQ GLEWIGYINPYNDVTKYNEKFKGRVTITRDTSAS TAYMELSSLRSEDTAVYYCARGSYYDYDGFVY WGQGTLVTVSSS TCR HEBE 53e.l EVQLLESGGGLVQPGGSLRLSCAASGYKFTSYV 66 MHWVKQAPGKGLEWIGYINPYNDVTKYNEKFK GKATLSRDNSKNTLYLQMNSLRAEDTAVHYCA RGSYYDYDGFVYWGQGTLVTVS S GGGGSGGGG SGGGGSSDIQMTQSPSTLSASVGDRVTMTCSATS SVSYMHWYQQKPGKAPKRWIYDTSKLASGVPA RFIGSGSGTEFTLTISSLQPDDFATYYCQQWSSNP LTFGGGTKVEIKS TCR HEBE 53e.2 D1QMTQSPSTLSASVGDRVTMTCSATSSVSYMH 67 WYQQKPGKAPKRWIYDTSKLASGVPARFIGSGS GTEFTLTIS SLQPDDF ATYYCQQ WS SNPLTFGGG TKVEIKGGGGAGGGGAGGGGSSEVQLLESGGGL VQPGGSLRLSCAASGYKFTSYVMHWVKQAPGK GLEWIGYINPYNDVTKYNEKFKGKATLSRDNSK NTLYLQMNSLRAEDTAVHYCARGSYYDYDGFV YWGQGTLVTVSSS TCR HEBE Hl 0 53f.l EVQLQQSGPELVKPGASVKMSCKASGYKFTSYV 68 MHWVKQAPGKGLEWIGYINPYNDVTKYNEKFK GKATLSRDNSKNTLYLQMNSLRAEDTAVHYCA RGSYYDYDGFVYWGQGTLVTVS S GGGGSGGGG AGGGGSSDIQMTQSPSTLSASVGDRVTMTCSATS SVSYMHWYQQKPGKAPKRWIYDTSKLASGVPA RFIGSGSGTEFTLTISSLQPDDFATYYCQQWSSNP LTFGGGTKVEIKS TCR HEBE Hl 0 53f.2 DIQMTQSPSTLSASVGDRVTMTCSATSSVSYMH 69 WYQQKPGKAPKRWIYDTSKLASGVPARFIGSGS GTEFTLTIS SLQPDDF ATYYCQQWS SNPLTFGGG TKVEIKGGGGAGGGGAGGGGASEVQLQQSGPEL VKPGASVKMSCKASGYKFTSYVMHWVKQAPG KGLEWIGYINPYNDVTKYNEKFKGKATLSRDNS KNTLYLQMNSLRAEDTAVHYCARGSYYDYDGF VYWGQGTLVTVSSS TCR HEBE H66 53g.l EVQLLQSGGGLVQPGGSLRLSCAASGYKFTSYV 70 MHWVRQAPGKGLEWVGYINPYNDVTKYNEKF KGRFTLSRDNSKNTLYLQMNSLRAEDTAVYYC ARGSYYDYDGFVYWGQGTLVTVSS GGGGSGGG GSGGGGSSDIQMTQSPSTLSASVGDRVTMTCSATSSVSYMHWYQQKPGKAPKRWIYDTSKLASGV45IPTS / 200318117.8Attorney Docket No.: AZL-004WOTarget Clone name scFv scFv sequence (AA) SEQ ID:Ref.PARFIGSGSGTEFTLTISSLQPDDFATYYCQQWSS NPLTFGGGTKVEIKS TCR HEBE H66 53g.2 DIQMTQSPSTLSASVGDRVTMTCSATSSVSYMH 71 WYQQKPGKAPKRWIYDTSKLASGVPARFIGSGS GTEFTLTISSLQPDDFATYYCQQWSSNPLTFGGG TKVEIKGGGGSGGGGAGGGGSSEVQLLQSGGGL VQPGGSLRLSCAASGYKFTSYVMHWVRQAPGK GLEWVGYINPYNDVTKYNEKFKGRFTLSRDNSK NTLYLQMNSLRAEDTAVYYCARGSYYDYDGFVYWGQGTLVTVSSS

[0130] In some embodiments, the targeting moiety comprises an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to an scFv amino acid sequence selected from those listed in Table 1. In some embodiments, the targeting moiety comprises an scFv amino acid sequence selected from those listed in Table 1.

[0131] In some embodiments, the targeting moiety comprises an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to an scFv amino acid sequence selected from those listed in Table 1, a CD8a stalk domain of SEQ ID NO: 1, and a CD8a transmembrane domain of SEQ ID NO: 2. In some embodiments, the targeting moiety comprises an scFv amino acid sequence selected from those listed in Table 1, a CD8a stalk domain of SEQ ID NO: 1, and a CD8a transmembrane domain of SEQ ID NO: 2.

[0132] In some embodiments, the antigen binding domain includes a heavy-chain variable region including a heavy-chain complementarity determining region 1 (CDR-H1), a heavy-chain complementarity determining region 2 (CDR-H2), and a heavy-chain complementarity determining region 3 (CDR-H3) of the amino acid sequence EVKLLESGGGLVQPKGSLKLSCAASGFTFNTYAMNWVRQAPGKGLEWVARIRSKYNN YATYYADSVKDRFTISRDDSQSILYLQMNNLKTEDTAMYYCVRHGNFGNSYVSWFAY WGQGTLVTVS (SEQ ID NO: 86); and a light-chain variable region including a light-chain complementarity determining region 1 (CDR-L1), a light-chain complementarity determining region 2 (CDR-L2), and a light-chain complementarity' determining region 3 (CDR-L3) of the amino acid sequence QAVVTQESALTTSPGETVTLTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTNKRAPG VPARFSGSLIGDKAALTITGAQTEDEAIYFCALWYSNLWVFGGGTKLTVL (SEQ ID NO: 87).

[0133] In some embodiments, the antigen binding domain includes a heavy -chain variable region including the amino acid sequence as set forth in SEQ ID NO: 86 and a light-chain46IPTS / 200318117.8Attorney Docket No.: AZL-004WOvariable region including the amino acid sequence as set forth in SEQ ID NO: 87. In some embodiments, the antigen binding domain includes the amino acid sequence as set forth in SEQ ID NO: 15. In some embodiments, the antigen binding domain includes the amino acid sequence as set forth in SEQ ID NO: 16.

[0134] In some embodiments, the targeting moiety comprises three heavy chain CDR sequences, CDR-H1. CDR-H2, and CDR-H3 and three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3 with amino acid sequences selected from those listed in Table 2, a CD8a stalk domain of SEQ ID NO: 1, and a CD8a transmembrane domain of SEQ ID NO: 2.Exemplary CDR sequences are provided below in Table 2.

[0135] In an embodiment, the CDR-H1 comprises the sequence set forth in SEQ ID NO: 136, CDR-H2 comprises the sequence set forth in SEQ ID NO: 137, CDR-H3 comprises the sequence set forth in SEQ ID NO: 138, CDR-L1 comprises the sequence set forth in SEQ ID NO: 139, CDR-L2 comprises the sequence set forth in SEQ ID NO: 140, and CDR-L3 comprises the sequence set forth in SEQ ID NO: 141, according to Kabat.

[0136] In an embodiment, the CDR-H1 comprises the sequence set forth in SEQ ID NO: 142, CDR-H2 comprises the sequence set forth in SEQ ID NO: 143, CDR-H3 comprises the sequence set forth in SEQ ID NO: 144, CDR-L1 comprises the sequence set forth in SEQ ID NO: 145. CDR-L2 comprises the sequence set forth in SEQ ID NO: 146, and CDR-L3 comprises the sequence set forth in SEQ ID NO: 147, according to Chothia.

[0137] In an embodiment, the CDR-H1 comprises the sequence set forth in SEQ ID NO: 148, CDR-H2 comprises the sequence set forth in SEQ ID NO: 149, CDR-H3 comprises the sequence set forth in SEQ ID NO: 150, CDR-L1 comprises the sequence set forth in SEQ ID NO: 151, CDR-L2 comprises the sequence set forth in SEQ ID NO: 152, and CDR-L3 comprises the sequence set forth in SEQ ID NO: 153, according to IMGT.

[0138] In an embodiment, the CDR-H1 comprises the sequence set forth in SEQ ID NO: 154, CDR-H2 comprises the sequence set forth in SEQ ID NO: 155, CDR-H3 comprises the sequence set forth in SEQ ID NO: 156, CDR-L1 comprises the sequence set forth in SEQ ID NO: 157, CDR-L2 comprises the sequence set forth in SEQ ID NO: 158, and CDR-L3 comprises the sequence set forth in SEQ ID NO: 159, according to North.

[0139] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising a VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%. or 100% identical to a sequence set forth in SEQ ID NO: 86, and the VL sequence at least47IPTS / 200318117.8Attorney Docket No.: AZL-004WO90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 87.

[0140] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 86, and the VL sequence set forth in SEQ ID NO: 87.

[0141] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising an scFv at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 16 or 15.

[0142] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the scFv sequence set forth in SEQ ID NO: 16 or 15.

[0143] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 86, and a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2. and CDR-L3, of the VL sequences set forth in SEQ ID NO: 87. optionally wherein CDR-H1, CDR-H2, CDR-H3. CDR-LL CDR-L2. and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 86 and SEQ ID NO: 87, respectively.

[0144] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 72, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 73, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 72 and SEQ ID NO: 73, respectively.

[0145] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl. CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 74, and a VL chain sequence comprising three light chain CDR sequences, CDR-LL CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 75, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 74 and SEQ ID NO: 75, respectively.

[0146] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-48IPTS / 200318117.8Attorney Docket No.: AZL-004WOHl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 76, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 77, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1. CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 76 and SEQ ID NO: 77. respectively.

[0147] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 78, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 79, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-LL CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 78 and SEQ ID NO: 79, respectively.

[0148] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 80, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 81, optionally wherein CDR-H1, CDR-H2. CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 80 and SEQ ID NO: 81, respectively.

[0149] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl. CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 82, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2. and CDR-L3, of the VL sequences set forth in SEQ ID NO: 83, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 82 and SEQ ID NO: 83, respectively.

[0150] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl. CDR-H2, and CDR-H3. of the VH sequences set forth in SEQ ID NO: 84, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 85, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 84 and SEQ ID NO: 85. respectively.49IPTS / 200318117.8Attorney Docket No.: AZL-004WO

[0151] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD4 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 88, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 89, optionally wherein CDR-H1, CDR-H2. CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 88 and SEQ ID NO: 89, respectively.

[0152] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD28 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl. CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 90, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2. and CDR-L3, of the VL sequences set forth in SEQ ID NO: 91, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 90 and SEQ ID NO: 91, respectively.

[0153] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD28 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl. CDR-H2, and CDR-H3. of the VH sequences set forth in SEQ ID NO: 92, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 93, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 92 and SEQ ID NO: 93. respectively.

[0154] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD28 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 94, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 95, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-LL CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 94 and SEQ ID NO: 95, respectively.

[0155] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 96, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 97, optionally wherein CDR-H1, CDR-H2, CDR-H3,50IPTS / 200318117.8Attorney Docket No.: AZL-004WOCDR-LL CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 96 and SEQ ID NO: 97, respectively.

[0156] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 98, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 99, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 98 and SEQ ID NO: 99, respectively.

[0157] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl. CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 100, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 101, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 100 and SEQ ID NO: 101, respectively.

[0158] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences. CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 100, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 102, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 100 and SEQ ID NO: 102, respectively.

[0159] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 103, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 104, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-LL CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 103 and SEQ ID NO: 104, respectively.

[0160] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 105, and a VL chain51IPTS / 200318117.8Attorney Docket No.: AZL-004WOsequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 101, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 105 and SEQ ID NO: 101, respectively.

[0161] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences. CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 105, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 102, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-LL CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 105 and SEQ ID NO: 102, respectively.

[0162] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD7 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 106, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 107, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-LL CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 106 and SEQ ID NO: 107, respectively.

[0163] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD7 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 108, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 109. optionally wherein CDR-H1, CDR-H2, CDR-H3. CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 108 and SEQ ID NO: 109, respectively.

[0164] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl. CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 110, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2. and CDR-L3, of the VL sequences set forth in SEQ ID NO: 111, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 110 and SEQ ID NO: 111, respectively.52IPTS / 200318117.8Attorney Docket No.: AZL-004WO

[0165] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 112, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 113. optionally wherein CDR-H1, CDR-H2, CDR-H3. CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 112 and SEQ ID NO: 113, respectively.

[0166] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl. CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 114, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2. and CDR-L3, of the VL sequences set forth in SEQ ID NO: 115, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 114 and SEQ ID NO: 115, respectively.

[0167] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl. CDR-H2, and CDR-H3. of the VH sequences set forth in SEQ ID NO: 116, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 117, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 116 and SEQ ID NO: 117, respectively.

[0168] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 118, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 119, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-LL CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 118 and SEQ ID NO: 119, respectively.

[0169] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 120, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 121. optionally wherein CDR-H1, CDR-H2, CDR-H3,53IPTS / 200318117.8Attorney Docket No.: AZL-004WOCDR-LL CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 120 and SEQ ID NO: 121, respectively.

[0170] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 122, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 123, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 122 and SEQ ID NO: 123, respectively.

[0171] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl. CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 124, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 125, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 124 and SEQ ID NO: 125, respectively.

[0172] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds TCR and comprises a VH chain sequence comprising three heavy chain CDR sequences. CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 126, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 127, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 126 and SEQ ID NO: 127, respectively.

[0173] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds TCR and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 128, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 129, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-LL CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 128 and SEQ ID NO: 129, respectively.

[0174] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds TCR and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 130, and a VL chain54IPTS / 200318117.8Attorney Docket No.: AZL-004WOsequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 129, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 130 and SEQ ID NO: 129, respectively.

[0175] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds TCR and comprises a VH chain sequence comprising three heavy chain CDR sequences. CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 131, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 129, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-LL CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 131 and SEQ ID NO: 129, respectively.

[0176] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds TCR and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 132, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 133, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-LL CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 132 and SEQ ID NO: 133, respectively.

[0177] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds TCR and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 134, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 133. optionally wherein CDR-H1, CDR-H2, CDR-H3. CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 134 and SEQ ID NO: 133, respectively.

[0178] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds TCR and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-Hl. CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 135, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2. and CDR-L3, of the VL sequences set forth in SEQ ID NO: 133, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 135 and SEQ ID NO: 133, respectively.55IPTS / 200318117.8Attorney Docket No.: AZL-004WO

[0179] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 86, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 87.

[0180] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 72, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 73.

[0181] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 74, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 75.

[0182] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 76, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 77.

[0183] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 78, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 79.

[0184] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 80, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 81.

[0185] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence at least 90%, 91%. 92%. 93%, 94%, 95%, 96%. 97%. 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 82, and the VL sequence at least56IPTS / 200318117.8Attorney Docket No.: AZL-004WO90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 83.

[0186] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 84, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 85.

[0187] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD4 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 88, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 89.

[0188] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD28 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 90, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 91.

[0189] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD28 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%. or 100% identical to a sequence set forth in SEQ ID NO: 92, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 93.

[0190] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD28 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 94, and the VL sequence at least 90%. 91%. 92%. 93%. 94%. 95%. 96%. 97%. 98%. 99%. or 100% identical to a sequence set forth in SEQ ID NO: 95.

[0191] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 96, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 97.57IPTS / 200318117.8Attorney Docket No.: AZL-004WO

[0192] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 98, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 99.

[0193] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 100, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 101.

[0194] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 100, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 102.

[0195] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 103. and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 104.

[0196] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 105, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 101.

[0197] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 105, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 102.

[0198] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD7 comprising the VH sequence at least 90%, 91%. 92%. 93%, 94%, 95%, 96%. 97%. 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 106, and the VL sequence at least58IPTS / 200318117.8Attorney Docket No.: AZL-004WO90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 107.

[0199] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD7 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 108, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 109.

[0200] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 110, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 111.

[0201] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 112, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 113.

[0202] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%. or 100% identical to a sequence set forth in SEQ ID NO: 114. and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 115.

[0203] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 116. and the VL sequence at least 90%. 91%. 92%. 93%. 94%. 95%. 96%. 97%. 98%. 99%. or 100% identical to a sequence set forth in SEQ ID NO: 117.

[0204] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 118, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 119.59IPTS / 200318117.8Attorney Docket No.: AZL-004WO

[0205] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 120, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 121.

[0206] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 122, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 123.

[0207] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 124, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 125.

[0208] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 126. and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 127.

[0209] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 128, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 129.

[0210] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 130, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 129.

[0211] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence at least 90%. 91%. 92%. 93%. 94%. 95%. 96%. 97%. 98%.99%, or 100% identical to a sequence set forth in SEQ ID NO: 131, and the VL sequence at least60IPTS / 200318117.8Attorney Docket No.: AZL-004WO90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 129.

[0212] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 132, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 133.

[0213] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 134, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 133.

[0214] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence at least 90%. 91%. 92%. 93%. 94%. 95%. 96%. 97%. 98%.99%, or 100% identical to a sequence set forth in SEQ ID NO: 135, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 133.

[0215] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 86, and the VL sequence set forth in SEQ ID NO: 87.

[0216] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 72, and the VL sequence set forth in SEQ ID NO: 73.

[0217] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 74, and the VL sequence set forth in SEQ ID NO: 75.

[0218] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 76, and the VL sequence set forth in SEQ ID NO: 77.

[0219] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 78, and the VL sequence set forth in SEQ ID NO: 79.61IPTS / 200318117.8Attorney Docket No.: AZL-004WO

[0220] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 80, and the VL sequence set forth in SEQ ID NO: 81.

[0221] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 82, and the VL sequence set forth in SEQ ID NO: 83.

[0222] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 84, and the VL sequence set forth in SEQ ID NO: 85.

[0223] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD4 comprising the VH sequence set forth in SEQ ID NO: 88, and the VL sequence set forth in SEQ ID NO: 89.

[0224] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD28 comprising the VH sequence set forth in SEQ ID NO: 90, and the VL sequence set forth in SEQ ID NO: 91.

[0225] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD28 comprising the VH sequence set forth in SEQ ID NO: 92, and the VL sequence set forth in SEQ ID NO: 93.

[0226] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD28 comprising the VH sequence set forth in SEQ ID NO: 94, and the VL sequence set forth in SEQ ID NO: 95.

[0227] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence set forth in SEQ ID NO: 96, and the VL sequence set forth in SEQ ID NO: 97.

[0228] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence set forth in SEQ ID NO: 98, and the VL sequence set forth in SEQ ID NO: 99.

[0229] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence set forth in SEQ ID NO: 100, and the VL sequence set forth in SEQ ID NO: 101.62IPTS / 200318117.8Attorney Docket No.: AZL-004WO

[0230] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence set forth in SEQ ID NO: 100, and the VL sequence set forth in SEQ ID NO: 102.

[0231] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence set forth in SEQ ID NO: 103, and the VL sequence set forth in SEQ ID NO: 104.

[0232] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence set forth in SEQ ID NO: 105, and the VL sequence set forth in SEQ ID NO: 101.

[0233] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence set forth in SEQ ID NO: 105, and the VL sequence set forth in SEQ ID NO: 102.

[0234] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD7 comprising the VH sequence set forth in SEQ ID NO: 106, and the VL sequence set forth in SEQ ID NO: 107.

[0235] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD7 comprising the VH sequence set forth in SEQ ID NO: 108, and the VL sequence set forth in SEQ ID NO: 109.

[0236] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 110, and the VL sequence set forth in SEQ ID NO: 111.

[0237] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 112, and the VL sequence set forth in SEQ ID NO: 113.

[0238] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 114. and the VL sequence set forth in SEQ ID NO: 115.

[0239] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 11, and the VL sequence set forth in SEQ ID NO: 117.63IPTS / 200318117.8Attorney Docket No.: AZL-004WO

[0240] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 118, and the VL sequence set forth in SEQ ID NO: 119.

[0241] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 120, and the VL sequence set forth in SEQ ID NO: 121.

[0242] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 122. and the VL sequence set forth in SEQ ID NO: 123.

[0243] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 124, and the VL sequence set forth in SEQ ID NO: 125.

[0244] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence set forth in SEQ ID NO: 126, and the VL sequence set forth in SEQ ID NO: 127.

[0245] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence set forth in SEQ ID NO: 128, and the VL sequence set forth in SEQ ID NO: 129.

[0246] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence set forth in SEQ ID NO: 130, and the VL sequence set forth in SEQ ID NO: 129.

[0247] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence set forth in SEQ ID NO: 131, and the VL sequence set forth in SEQ ID NO: 129.

[0248] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence set forth in SEQ ID NO: 132, and the VL sequence set forth in SEQ ID NO: 133.

[0249] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence set forth in SEQ ID NO: 134, and the VL sequence set forth in SEQ ID NO: 133.64IPTS / 200318117.8Attorney Docket No.: AZL-004WO

[0250] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence set forth in SEQ ID NO: 135, and the VL sequence set forth in SEQ ID NO: 133.

[0251] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising an scFv at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence selected from SEQ ID NOs: 3-14.

[0252] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD5 comprising an scFv at least 90%. 91%. 92%. 93%. 94%. 95%. 96%. 97%. 98%. 99%. or 100% identical to a sequence selected from SEQ ID NOs: 24-37.

[0253] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD7 comprising an scFv at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence selected from SEQ ID NOs: 38-40.

[0254] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 comprising an scFv at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence selected from SEQ ID NOs: 42-57.

[0255] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD4 comprising an scFv at least 90%. 91%. 92%. 93%. 94%. 95%. 96%. 97%. 98%. 99%. or 100% identical to a sequence selected from SEQ ID NOs: 17-18.

[0256] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD28 comprising an scFv at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence selected from SEQ ID NOs: 19-23.

[0257] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds TCR comprising an scFv at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence selected from SEQ ID NOs: 58-71.

[0258] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD3 comprising an scFv having the sequence set forth in SEQ ID NOs: 3-14.

[0259] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD5 comprising an scFv having the sequence set forth in SEQ ID NOs: 24-37.

[0260] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD7 comprising an scFv having the sequence set forth in SEQ ID NOs: 38-40.

[0261] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD27 comprising an scFv having the sequence set forth in SEQ ID NOs: 42-57.65IPTS / 200318117.8Attorney Docket No.: AZL-004WO

[0262] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD4 comprising an scFv having the sequence set forth in SEQ ID NOs: 17-18.

[0263] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds CD28 comprising an scFv having the sequence set forth in SEQ ID NOs: 19-23.

[0264] In an embodiment, the antibody or antigen-binding fragment thereof specifically binds TCR comprising an scFv having the sequence set forth in SEQ ID NOs: 58-71.

[0265] In some embodiments, a deli x ery particle comprises (a) a targeting moiety on the surface of the particle, wherein the targeting moiety comprises a means for binding a T cell antigen; and (b) a payload encapsidated within the particle.

[0266] In some embodiments, the a delivery particle comprises (a) a targeting moiety' on the surface of the a targeting moiety on the surface of the particle, wherein the targeting moiety comprises a means for binding a T cell antigen selected from the group consisting of: CD3, CD5, CD7, CD4, CD28, TCR and CD27; and (b) a payload encapsidated within the particle. Table 2. CDR Sequences of SP34-2 Clone 7kCDR Rabat Chothia IMGT North CDR-H1 TYAMN GFTFNTY GFTFNTYA AASGFTFNTYAM (SEQ ID NO: 136) (SEQ ID NO: 142) (SEQ ID NO: 148) N(SEQ ID NO: 154) CDR-H2 RIRSKYNNYAT RSKYNNYA IRSKYNNYAT RIRSKYNNYATY YYADSVKD (SEQ ID NO: 143) (SEQ ID NO: 149) (SEQ ID NO: 155) (SEQ ID NO: 137)CDR-H3 HGNFGNSYVSW HGNFGNSYVSWF VRHGNFGNSYVS VRHGNFGNSYVS FAY AY WFAY WFAY(SEQ ID NO: 138) (SEQ ID NO: 144) (SEQ ID NO: 150) (SEQ ID NO: 156) CDR-L1 RSSTGAVTTSNY RSSTGAVTTSNYA TGAVTTSNY SSTGAVTTSNYAN AN N (SEQ ID NO: 151) (SEQ ID NO: 157) (SEQ ID NO: 139) (SEQ ID NO: 145)CDR-L2 GTNKRAP GTNKRAP GTN GGTNKRAP (SEQ ID NO: 140) (SEQ ID NO: 146) (SEQ ID NO: 152) (SEQ ID NO: 158) CDR-L3 ALWYSNLWV ALWYSNLWV ALWYSNLWV ALWYSNLWV(SEQ ID NO: 141) (SEQ ID NO: 147) (SEQ ID NO: 153) (SEQ ID NO: 159)Pharmaceutical compositions

[0267] Methods for treatment of cancer diseases are also encompassed by the present invention. Said methods of the invention include administering a therapeutically effective amount of a genomic editing system. The genomic editing system of the invention can be formulated in pharmaceutical compositions. These compositions can include, in addition to one or more of the viral vectors, a pharmaceutically acceptable excipient, carrier, buffer, stabiliser or other66IPTS / 200318117.8Attorney Docket No.: AZL-004WOmaterials well known to those skilled in the art. Such materials should be non-toxic and should not interfere with the efficacy of the active ingredient. The precise nature of the carrier or other material can depend on the route of administration, e.g. oral, intravenous, cutaneous or subcutaneous, nasal, intramuscular, intraperitoneal routes.

[0268] In some embodiments, are methods of delivering a pay load to a population of target cells comprising contacting the population of target cells with a particle described herein. In some embodiments, are methods of editing a population of target cells comprising contacting the population of target cells with a particle described herein. In some embodiments, are methods of modifying a population of target cells to express a transgene comprising contacting the population of target cells with a particle described herein.

[0269] For intravenous, cutaneous or subcutaneous injection, or injection at the site of affliction, the active ingredient will be in the form of a parenterally acceptable aqueous solution which is pyrogen-free and has suitable pH, isotonicity and stability. Those of relevant skill in the art are well able to prepare suitable solutions using, for example, isotonic vehicles such as Sodium Chloride Injection, Ringer's Injection, Lactated Ringer's Injection. Preservatives, stabilisers, buffers, antioxidants and / or other additives can be included, as required.

[0270] A pharmaceutically useful compound according to the present invention that is to be given to an individual, is preferably administered in a “therapeutically effective amount”, this being sufficient to show benefit to the individual. The actual amount administered, and rate and time-course of administration, will depend on the nature and severity of protein aggregation disease being treated. Prescription of treatment, e.g. decisions on dosage etc, is within the responsibility of general practitioners and other medical doctors and typically takes account of the disorder to be treated, the condition of the individual patient, the site of delivery, the method of administration and other factors known to practitioners. Examples of the techniques and protocols mentioned above can be found in Remington's Pharmaceutical Sciences, 16th edition, Osol, A. (ed), 1980.

[0271] A composition can be administered alone or in combination with other treatments, either simultaneously or sequentially dependent upon the condition to be treated.EXAMPLESExample 1: Materials and methods

[0272] Cell models: Three cell models were used to test the specificity and efficacy of scFv-targeted delivery particles (e.g., a VLP): (i) Jurkats, (ii) HEK293T cells expressing human ligands, and (iii) HEK293T cells expressing non-human primate (NHP) ligands.67IPTS / 200318117.8Attorney Docket No.: AZL-004WO

[0273] Jurkats express most of the target ligands evaluated in these experiments, including CD5, CD7, TCR, CD4, CD28, and CD3. Jurkats do not express CD27. See FIG. 1. HEK293T cells were engineered to overexpress human or NHP target ligands CD5, CD7, CD27, TCR, CD4, CD28, CD3, and CD 19 and EGFP. Engineered cells were then mixed at a 1: 1 to 10: 1 ratio with wildtype cells (ligand negative, EGFP negative). In this system. GFP expression was used as a proxy for on-target (GFP+) delivery vs. off-target (GFP-) delivery. See FIG. 2 and FIG.3.

[0274] Delivery Particles: delivery particles were constructed according to known methods (See WO 2020 / 102709) and comprised a Gag-Cas9 fusion protein complexed with an sgRNA targeting the B2M gene. Briefly, 3.5-4 million Lenti-X cells w ere seeded into 10 cm tissue culture dishes and transfected the next day with plasmid encoding the WT VSV-G protein or mutant version (VSV-GMut). a plasmid encoding the Gag-Cas9 fusion protein, a plasmid encoding the Gag-Pol polyprotein, and a plasmid encoding a B2M sgRNA using polyethylenimine (Polysciences Inc.) at a 3: 1 PEEplasmid ratio. Two days post-transfection, Cas9-delivery particle containing supernatants were harvested and passed through a 0.45pm PES syringe filter and concentrated with Lenti-X Concentrator according to the manufacturer's instructions. Concentrated Cas9-deli very particles were resuspended in Opti-MEM (Gibco), SFEM II (StemCell) or T cell media at a final concentration of lOx. The Cas9-deli very particles were then either stored at 4°C or frozen at -80°C within an isopropanol-filled freezing container until use. Cas9-delivery particle and lentiviral samples were titered using a QuickTiter™ Lentivirus Titer Kit (Lentivirus-Associated HIV p24) (CellBio Labs) according to the manufacturer's instructions. Where indicated, the delivery particles additionally comprises a lentiviral mCherry transgene. Controls included a CD19-targeted scFv delivery' particle (nonspecific targeting), a WT VSV-G pseudotyped delivery particle (broad tropism), CD3 / 4 / 28-targeted delivery particles (described previously in Hamilton et al.), or untransduced (UT) cells.

[0275] Targeting Moieties: Additional targeted Cas9-delivery particles were produced in the same way as VSV-G Cas9-delivery particles, except that an additional targeting moiety plasmid was included during transfection. A panel of scFvs targeting different T cell ligands were selected. The targeting moieties comprised an scFv, a CD8a stalk, and a CD8a transmembrane domain. See Table A below for the sequence information for each scFv and targeting moiety comprising the same. A schematic of the particles is shown in FIG. 4.Table A. Exemplary Amino acid sequences for scFvs and corresponding targeting moieties Target antigen scFv Ref.CD28 15b.1CD28 15b.2CD28 15c.168IPTS / 200318117.8Attorney Docket No.: AZL-004WOTarget antigen scFv Ref.CD28 15c.2CD5 50a.1CD5 50a.2CD5 50b.1CD5 50b.2CD5 50c.1CD5 50c.2CD5 50d.lCD5 50d.2CD5 50e.lCD5 50e.2CD5 50f.1CD5 50f.2CD5 50g.1CD5 50g.2CD7 51a.lCD7 51a.2CD7 51b.1CD7 51b.2CD27 52a.1CD27 52a.2CD27 52b.1CD27 52b.2CD27 52c.1CD27 52c.2CD27 52d.lCD27 52d.2CD27 52e.lCD27 52e.2CD27 52f.lCD27 52f.2CD27 52g.1CD27 52g.2CD27 52h.lCD27 52h.2TCR 53a.1TCR 53a.2TCR 53b.1TCR 53b.2TCR 53c.1TCR 53c.2TCR 53d.1TCR 53d.2TCR 53e.lTCR 53e.2TCR 53f.1TCR 53f.2TCR 53g.1TCR 53g.2CD3 7aCD3 7bCD3 7f69 IPTS / 200318117.8Attorney Docket No.: AZL-004WOTarget antigen scFv Ref.7f.lCD3 Acapatamab7f.2CD3 AcapatamabCD3 7a.1 UCHT1CD3 7a.2 UCHTlCD3 7h.l OKT3CD3 711.2 OKT3CD3 7i.l hOTK3CD3 7i.2 hOKT3CD3 7j.l FN-18CD3 7j.2 FN-18CD3 7k.1 SP34-2CD3 7k.2 SP34-2CD4 9a.1CD4 9a.2CD19 CD19CD3 / 4 / 28 CD3 / 4 / 28

[0276] Culture methods: Cells were plated at 15,000 / well (Jurkat), 15,000 / well (engineered human HEK), or 15,000 / well (engineered NHP HEK) in 96-well plates. Concentrated delivery7particles (volumes indicated below) were simultaneously added to the wells and transgene integration and / or editing efficiencies were assayed 3-5 days post treatment. Integration efficiency was measured by FACS for stable mCherry integration. Editing efficiency was measured by FACS for the B2M protein (loss of B2M surface expression indicative of an edited locus).

[0277] Flow cytometry: To assess genome editing via flow cytometry', cells were stained with an anti -human B2M-APC antibody (316312, Biolegend), an anti -human B2M-PE antibody (316306, Biolegend), or an anti-human TCR-APC antibody (306718, Biolegend) in PBS containing 1% bovine serum albumin and an Attune NxT flow cytometer with 96-well autosampler (Thermo Fisher Scientific) was used for flow cytometry analysis. Ligand expression was confirmed for engineered HEK cells using anti-human CD28-PE antibody (302907, Biolegend), anti-human CD20-PE antibody (302306, Biolegend), anti-human CD4-PE-Cyanine7 antibody (300512, Biolegend) and anti-human CD19-PE antibody (302208, Biolegend). Immune cell phenotyping was performed with anti-human CD4-FITC antibody (300538, Biolegend), anti-human CD8-PE-Cy7 antibody (344711, Biolegend), anti-human CD45-PE-Cy7 antibody (368531, Biolegend), and anti-human CD19-FITC antibody (302206, Biolegend). Data analysis was performed using Flow Jo vlO 10.7.1 (FlowJo, LLC, Ashland OR). APC: allophycocyanin. PE: phycoerythrin. FITC: fluorescein isothiocyanate.70IPTS / 200318117.8Attorney Docket No.: AZL-004WOExample 2. Identification of scFvs that increase delivery efficiency of Cas9-delivery particles

[0278] Purpose: This study sought to identify T-cell targeting scFvs (CD5, CD7, CD27, CD28, or TCR) that resulted in improved deliver}' of Cas9-delivery particles.

[0279] Methods: For this study, a panel of T cell-targeting scFvs was screened using the Jurkat and engineered HEK cells described above. For Jurkat experiments, cells were treated with 100 pL of Cas9-delivery particles comprising an mCherry lentiviral transgene to assess levels of transgene integration and editing. For HEK experiments, cells were treated with 5 pL of Cas9-delivery particles comprising an mCherry lentiviral transgene to assess levels of transgene integration and editing. On-target and off-target transgene integration and editing were measured using the HEK cells. On-target integration and editing were measured as percent mCheny+ in GFP+ cells. For CD3 / TCR, integration was measured as the percent mCherry in GFP+ / BFP+ cells. Off-target effects were measured as percent mCherry+ in GFP- cells. For CD3 / TCR, nonspecific integration was measured as percent mCherry in GFP- / BFP- cells.

[0280] Results: As shown, there was successful integration (FIGs. 5A and 6A) and editing (FIGs. 5B and 6B) with several of the constructs comprising targeting molecules that bind to CD3, CD4. CD28, CD5, CD7, TCR. and CD27 scFVs in both Jurkats (FIGs. 5A and 5B and Table B) and HEK293Ts (FIGs. 6A and 6B). Many of these constructs resulted in integration and editing efficiencies that were improved compared to prior scFv-targeting moieties (z.e., improved compared to CD3 / 4 / 28 targeted deliver}' particles ). For example, CD5-targeted deliver}' particles (e.g., 50a.l, 50a.2, 50c.l, 50c.2, 50d.l, 50d.2, 50e.l, 50e.2, 50f.l, 50g.2) CD7-targeted delivery particles (e.g., 51a.l. 51a.2, 51b.2), TCR-targeted delivery particles (e.g.. 53b.1, 53c.l), and CD27-targeted delivery particles (e.g. 52f.1, 52g.2, 52h.l, 52h.2) demonstrated improved transgene integration and editing efficiencies in HEK cells compared to CD3 / 4 / 28 targeted deliver}' particles, while maintaining low off target effects. The CD5 50a.1 and 50a.2 constructs had high percentages of integration and editing among both cell types. As shown in Table B, the CD5 50a.1 and 50a.2 constructs had greater than 3% integration and greater than 72% editing in Jurkat cells. Based on these results, the CD5, CD7, and CD27-targeted Cas9- deliver}' particle candidates identified to have the highest efficacy and specificity among both cell types were selected for further study.

[0281] Table B. Integration and Editing Percentages in Jurkat cells for various constructs Targeting Moiety (scFv% Mean Integration (n=3) % Mean Editing (n=3) Ref.)CD5 (50a.1) 3.57 72.03CD5 (50a.2) 3.12 72.3771IPTS / 200318117.8Attorney Docket No.: AZL-004WOCD5 (50b.1) 0.00 0.21 CD5 (50b.2) 0.01 0.31 CD5 (50c.1) 1.50 71.13 CD5 (50c.2) 1.28 70.03 CD5 (50d.l) 1.15 68.37 CD5 (50d.2) 1.78 71.83 CD5 (50e.l) 0.60 63.07 CD5 (50e.2) 1.80 72.80 CD5 (50f.l) 0.69 66.10 CD5 (50f.2) 1.76 71.93 CD5 (50g.1) 0.22 21.80 CD5 (50g.2) 1.49 72.50 CD7 (51a.1) 0.08 10.16 CD7 (51a.2) 0.91 52.43 CD7 (51b.1) 0.32 23.47 CD7 (51b.2) 0.49 37.97 CD27 (52a.1) 0.21 21.43 CD27 (52a.2) 0.22 20.53 CD27 (52b.1) 0.01 0.98 CD27 (52b.2) 0.00 1.00 CD27 (52c.1) 0.23 11.63 CD27 (52c.2) 0.21 13.73 CD27 (52d.l) 0.00 0.31 CD27 (52d.2) 0.00 0.49 CD27 (52e.l) 0.03 2.96 CD27 (52e.2) 0.05 14.37 CD27 (52f.l) 0.20 22.23 CD27 (52f.2) 0.08 11.26 CD27 (52g.1) 0.00 0.34 CD27 (52g.2) 0.02 1.11 CD27 (52h.l) 0.11 11.17 CD27 (52h.2) 0.14 16.67 TCR (53a.1) 0.95 67.53 TCR (53a.2) 0.11 22.30 TCR (53b.1) 1.69 69.67 TCR (53b.2) 0.28 50.03 TCR (53c.1) 0.90 64.23 TCR (53c.2) 0.50 54.50 TCR (53d.1) 0.58 48.73 TCR (53d.2) 0.40 52.17 TCR (53e.l) 0.00 0.53 TCR (53e.2) 0.02 2.45 TCR (53f.1) 0.32 34.77TCR (53f.2) 0.59 62.3772IPTS / 200318117.8Attorney Docket No.: AZL-004WOTCR (53g.1) 0.61 58.10TCR (53g.2) 0.31 37.67CD3 (7a) 0.22 35.57CD3 (7b) 0.00 0.19CD3 (7f) 0.11 7.13CD4 (9a.1) 0.08 18.10CD4 (9a,2) 0.07 16.13CD28 (15b.1) 0.23 21.77CD28 (15b.2) 0.47 43.07 CD28 (15c.l) 0.00 0.26CD28 (15c.2) 0.00 0.53 CD3 / 4 / 28 0.94 54.70CD19 0.00 0.29 VSVG 35.80 69.17UT 0.04 0.81Example 3. Higher doses of scFv-targeted delivery particles results in greater integration and editing among Jurkats and HEK293Ts

[0282] Purpose: This study sought to assess the dosage effects of the T cell scFv-targeted delivery particles identified in Example 2 on levels of transgene integration and editing in Jurkats and HEK293Ts.

[0283] Method: delivery’ particles packaging Cas9 RNP and an mCherry transgene were pseudotyped with different scFvs and VSV-Gmut, then used to transduce Jurkats in 2-fold dilutions. All delivery particles (scFv + VSVGmut) packaged Cas9 and a lentiviral transgene. The scFvs were selected from scFvs which demonstrated efficiency and specificity in Example 2. Jurkats were used to demonstrate on-target efficiency. Negative controls included CD19-targeted delivery particles (Jurkats do not express CD19). Positive controls included VSV-G pseudotyped delivery’ particles with broad tropism. The scFvs in Table C were further tested.Table C. ScFvs evaluated in dose titration studies.ScFv ConstructCD5 50a.1CD5 50a.2CD5 50c.2CD5 50d.2CD5 50e.2CD5 50f.2CD5 50g.173IPTS / 200318117.8Attorney Docket No.: AZL-004WOScFv ConstructCD5 50g.2CD7 51a.lCD7 51a.2CD28 15aCD28 15b.2CD3 / CD28 7f / 15b.2CD3 / CD4 / CD28 7f / 9a.l / 15b.2TCR 53a.lTCR 53a.2TCR 53b.lTCR 53b.2TCR 53g.2CD3 7aCD3 7a PDGFRCD3 7fCD3 7gCD19 CD19VSVG VSVG CD27 52h.lCD27 52h.2CD4 9a.1

[0284] Transgene integration and editing percentages were both calculated by the methods described in Example 2. Finally, an IC50 editing fold change was compared between scFvs of CD5 and CD7, and the more well known CD3, CD4 and CD28 scFvs. Similar experiments were performed with engineered HEKs. For the dose titration, a range of delivery particles volumes was evaluated from 0.5 pL to 128 pL.

[0285] Results: Results for integration in Jurkats are shown in FIGs. 7A-7F and Table D and results for editing in Jurkats are shown in FIGs. 8A-8F and Table E. Results for integration in HEK293Ts are shown in FIGs. 9A-9F and results for editing in HEK293Ts are shown in FIGs.10A-10F. As shown, a dose-dependent pattern was observed for CD3, CD5, CD7, TCR and CD27-targeted Cas9- delivery particles of interest in both Jurkats and HEK293Ts. The percentage of integration and editing consistently increased with the volume of delivery particles applied in both cell types. In addition, a comparison editing efficiency between select CD5- and CD7-targeted delivery particles and CD4 / CD28 targeted delivery particles is shown in Table F.74IPTS / 200318117.8Attorney Docket No.: AZL-004WOIn sum, scFv-targeted Cas9- deliver}' particles comprising scFv targeting molecules that bind to CD3, CD5, CD7, TCR, or CD27 demonstrated dose-dependent increases in integration and editing efficiencies.Table D. A comparison of % mean integration in Jurkats amongst various scFvs Targeting Moiety (scFvEDV Volume (uL) % Mean Integration (n=3) Ref.)90 7.4345 5.0222.5 4.1911.25 2.95CD5 (50a.1)5.63 1.722.81 1.011.41 0.500.7 0.2790 11.7745 6.9022.5 5.1111.25 3.58CD5 (50a.2)5.63 2.102.81 1.111.41 0.620.7 0.3890 4.1545 3.5022.5 3.5211.25 3.47CD5 (50c.2)5.63 2.982.81 2.251.41 1.400.7 0.8090 5.0245 4.5022.5 4.6811.25 4.70CD5 (50d.2)5.63 3.942.81 2.821.41 1.700.7 1.0590 4.49CD5 (50e.2) 45 3.9222.5 4.2875IPTS / 200318117.8Attorney Docket No.: AZL-004WO11.25 4.01 5.63 3.06 2.81 2.18 1.41 1.28 0.7 0.78 90 3.76 45 3.31 22.5 3.33 11.25 3.31 CD5 (50f.2)5.63 2.65 2.81 1.79 1.41 1.12 0.7 0.67 90 0.98 45 0.65 22.5 0.44 11.25 0.30 CD5 (50g.1)5.63 0.15 2.81 0.10 1.41 0.06 0.7 0.04 90 4.72 45 4.12 22.5 4.37 11.25 4.28 CD5 (50g.2)5.63 3.66 2.81 2.58 1.41 1.50 0.7 0.86 90 0.42 45 0.26 22.5 0.18 11.25 0.13 CD7 (51a.1)5.63 0.07 2.81 0.05 1.41 0.04 0.7 0.02 90 4.77 45 3.13 22.5 2.23 CD7 (51a.2) 11.25 1.495.63 0.85 2.81 0.451.41 0.2776IPTS / 200318117.8Attorney Docket No.: AZL-004WO0.7 0.16 90 5.49 45 2.60 22.5 1.50 11.25 0.99 TCR (53a.1)5.63 0.51 2.81 0.32 1.41 0.17 0.7 0.08 90 0.44 45 0.22 22.5 0.14 11.25 0.10 TCR (53a.2)5.63 0.04 2.81 0.03 1.41 0.02 0.7 0.03 90 8.55 45 3.98 22.5 2.23 11.25 1.31 TCR (53b.1)5.63 0.73 2.81 0.34 1.41 0.18 0.7 0.13 90 1.58 45 0.78 22.5 0.40 11.25 0.25 TCR (53b.2)5.63 0.13 2.81 0.09 1.41 0.05 0.7 0.03 90 1.69 45 0.67 22.5 0.39 11.25 0.21 TCR (53g.2)5.63 0.13 2.81 0.09 1.41 0.05 0.7 0.02 90 1.06 CD3 (7a) 45 0.5722.5 0.5577IPTS / 200318117.8Attorney Docket No.: AZL-004WO11.25 0.37 5.63 0.18 2.81 0.13 1.41 0.07 0.7 0.04 90 0.06 45 0.04 22.5 0.02 11.25 0.01 CD3 (7a PDGFR)5.63 0.01 2.81 0.00 1.41 0.01 0.7 0.01 90 0.41 45 0.24 22.5 0.16 11.25 0.10 CD3 (7f)5.63 0.05 2.81 0.04 1.41 0.02 0.7 0.02 90 0.53 45 0.46 22.5 0.35 11.25 0.24 CD3 (7f / 15b.2)5.63 0.15 2.81 0.11 1.41 0.05 0.7 0.03 90 1.00 45 0.78 22.5 0.63 11.25 0.42 CD3 (7f / 9a.l / 15b.2)5.63 0.27 2.81 0.19 1.41 0.12 0.7 0.06 90 0.58 45 0.40 22.5 0.22 CD3 (7g) 11.25 0.145.63 0.06 2.81 0.051.41 0.0378IPTS / 200318117.8Attorney Docket No.: AZL-004WO0.7 0.02 90 0.31 45 0.25 22.5 0.30 11.25 0.26 CD4 (9a.1)5.63 0.22 2.81 0.15 1.41 0.12 0.7 0.07 90 0.01 45 0.00 22.5 0.00 11.25 0.00 CD28 (15a)5.63 0.00 2.81 0.00 1.41 0.00 0.7 0.01 90 0.50 45 0.41 22.5 0.34 11.25 0.24 CD28 (15b.2)5.63 0.14 2.81 0.08 1.41 0.05 0.7 0.03 90 0.00 45 0.00 22.5 0.00 11.25 0.00 CD195.63 0.00 2.81 0.00 1.41 0.01 0.7 0.00 90 18.53 45 11.30 22.5 7.85 11.25 5.18 VSVG5.63 2.80 2.81 1.74 1.41 1.010.7 0.5579IPTS / 200318117.8Attorney Docket No.: AZL-004WOTable E. A comparison of % mean editing in Jurkats amongst various scFvs Targeting Moiety (scFvEDV Volume (uL) % Mean Editing (n=3) Ref.)90 68.90 45 69.07 22.5 68.13 11.25 60.23 CD5 (50a.1)5.63 48.97 2.81 36.80 1.41 21.33 0.7 8.4490 68.83 45 69.03 22.5 70.27 11.25 64.53 CD5 (50a.2)5.63 57.73 2.81 42.00 1.41 25.33 0.7 10.25 90 69.90 45 68.57 22.5 70.17 11.25 67.87 CD5 (50c.2)5.63 67.00 2.81 59.23 1.41 47.73 0.7 29.27 90 68.73 45 68.37 22.5 70.33 11.25 69.10 CD5 (50d.2)5.63 70.17 2.81 64.77 1.41 52.47 0.7 34.67 90 69.07 45 68.00 22.5 70.10 CD5 (50e.2)11.25 68.23 5.63 65.572.81 56.5380IPTS / 200318117.8Attorney Docket No.: AZL-004WO1.41 39.17 0.7 23.47 90 69.23 45 67.80 22.5 69.43 11.25 66.97 CD5 (50f.2)5.63 64.40 2.81 54.27 1.41 35.70 0.7 20.83 90 57.50 45 41.57 22.5 30.90 11.25 20.80 CD5 (50g.1)5.63 12.43 2.81 15.00 1.41 4.94 0.7 3.37 90 68.40 45 67.67 22.5 70.43 11.25 69.57 CD5 (50g.2)5.63 68.90 2.81 63.70 1.41 51.53 0.7 35.90 90 36.30 45 20.60 22.5 15.30 11.25 6.29 CD7 (51a.l)5.63 3.51 2.81 6.04 1.41 7.90 0.7 1.25 90 68.97 45 65.33 22.5 59.47 11.25 44.20 CD7 (51a.2)5.63 30.57 2.81 20.60 1.41 12.32 0.7 4.08 90 62.73 TCR (53a.1)45 57.5381IPTS / 200318117.8Attorney Docket No.: AZL-004WO22.5 46.30 11.25 30.20 5.63 17.80 2.81 9.63 1.41 4.60 0.7 2.93 90 32.03 45 14.50 22.5 9.56 11.25 7.39 TCR (53a.2)5.63 11.91 2.81 5.28 1.41 4.57 0.7 3.28 90 61.83 45 59.40 22.5 51.17 11.25 37.00 TCR (53b.1)5.63 22.00 2.81 14.93 1.41 11.97 0.7 3.08 90 54.13 45 34.23 22.5 20.27 11.25 9.66 TCR (53b.2)5.63 6.77 2.81 5.10 1.41 7.37 0.7 0.43 90 47.83 45 26.87 22.5 16.87 11.25 7.70 TCR (53g.2)5.63 10.19 2.81 7.84 1.41 5.77 0.7 1.63 90 42.17 45 27.43 22.5 17.70 CD3 (7a)11.25 10.37 5.63 11.032.81 3.8282IPTS / 200318117.8Attorney Docket No.: AZL-004WO1.41 3.75 0.7 1.53 90 6.02 45 1.84 22.5 5.23 11.25 7.10 CD3 (7a PDGFR)5.63 4.93 2.81 2.43 1.41 0.63 0.7 3.02 90 14.97 45 6.71 22.5 5.59 11.25 5.90 CD3 (7f)5.63 8.78 2.81 7.75 1.41 0.93 0.7 3.35 90 28.03 45 19.47 22.5 19.87 11.25 8.77 CD3 (71715b.2)5.63 11.24 2.81 2.91 1.41 4.21 0.7 0.43 90 52.33 45 37.83 22.5 33.00 11.25 20.40 CD3 (7f / 9a.l / 15b.2)5.63 19.43 2.81 6.75 1.41 3.55 0.7 0.94 90 48.47 45 26.60 22.5 17.03 11.25 9.54 CD3 (7g)5.63 4.36 2.81 3.21 1.41 3.36 0.7 7.49 90 23.87 CD4 (9a.1)45 18.7083IPTS / 200318117.8Attorney Docket No.: AZL-004WO22.5 19.10 11.25 19.57 5.63 18.27 2.81 12.93 1.41 7.48 0.7 7.25 90 0.41 45 2.69 22.5 6.18 11.25 5.46 CD28 (15a)5.63 2.87 2.81 2.50 1.41 5.65 0.7 0.76 90 25.37 45 18.10 22.5 19.90 11.25 9.90 CD28 (15b.2)5.63 11.60 2.81 5.32 1.41 5.26 0.7 0.37 90 1.45 45 0.22 22.5 4.38 11.25 5.90 CD195.63 3.29 2.81 2.36 1.41 2.21 0.7 0.66 90 68.73 45 68.33 22.5 70.30 11.25 68.43 VSVG5.63 62.67 2.81 48.47 1.41 30.300.7 15.9384IPTS / 200318117.8Attorney Docket No.: AZL-004WOTable F. A comparison of IC50 editing fold change amongst various scFvsscFv CDS CDS CDS CD5 CDS CD5 CDS CD5 CD7 CD7 (50a.l (50a.2 (50c.2 (50d.2 (50e.2 (50f.2 (50g.l (50g.2 (51a.l (51a.2 ) ) ) ) ) ) ) ) ) ) IC50 9.74 13.18 33.60 40.60 25.36 22.42 -0.95 42.31 N / A 3.05 editingfoldchange

[0286] Additional experiments were performed with engineered HEK293T cells overexpressing NHP ligands from cynomolgus monkeys (cyno) or pig-tailed macaques (pig-tailed). Integration and editing were assessed as described above. Results for integration are in FIGs. 11A and 11B, and results for editing are in FIGs. 12A and 12B. These findings demonstrate that the scFv-targeting moieties described herein are cross-reactive with NHP target molecules.Example 4: Targeted delivery particles can activate and deliver Cas9 for editing in resting human T cells and non-human primate T cells ex vivo

[0287] Additional CD3 and TCR scFvs were used to generate targeted delivery particles and the activation and editing of these targeted delivery particles were tested on human and NHP T cells. The scFvs tested in this experiment are shown in Table G.Table G: CD3 and TCR scFvsscFv ConstructTCR 53a.1CD3 7f.l AcapatamabCD3 7f.2 AcapatamabCD3 7a.1 UCHT1CD3 7a.2 UCHTlCD3 7h.l OKT3CD3 7h.2 OKT3CD3 7i.l hOTK3CD3 7i.2 hOKT3CD3 7j.l FN-18CD3 7j.2 FN-18CD3 7k.1 SP34-285IPTS / 200318117.8Attorney Docket No.: AZL-004WOscFv ConstructCD3 7k.2 SP34-2

[0288] Targeted delivery particles were either added to T cells unconcentrated, or lOOx concentrated via PEG precipitation. Flow cytometry measurements were taken 4 or 7 days after transduction. CD25+ was used as a marker for T cell activation. Cas9 was targeted to the B2M gene and B2M surface expression was used as a measure of genome editing. Results are shown in FIG. 13 - FIG. 15. These results demonstrate that the Cas9- delivery particles with scFvs targeting TCR or CD3 can potentially activate and edit resting T cells (See CD25% and B2M% in FIG. 13), as well as edit activated T cells (See B2M% in FIG. 14). Note that activation of T cells is transient. Without continued stimulation, CD25 expression is expected to decrease over time. As such, there is a steeper decline in CD25 expression between Day 4 and Day 7 in FIG.14 (activated T cells) as compared with the decline in FIG. 13 (resting T cells). Additionally, different scFvs targeting TCR or CD3 resulted in variable activation of resting primary human T cells in vitro (FIG. 13). For example, 7a.2 resulted in the greatest amount of activation at day 4, while 7k.2 was intermediate, and 7j.2 was lower. In both resting and activated primary human T cells, the B2M editing remained stable over time. As shown in FIG. 15, and quantified in Table H, constructs 7a.1, 7a.2, and 7k.2 all demonstrated editing efficiencies generally at least 2-fold greater (and for 7a.l and 7a.2 generally at least 3-fold greater) than all other constructs tested for editing resting human T cells.

[0289] Table H. A comparison of % TCR- and % CD25+ in resting Human T cells and NHP T cellsscFv Human T cells NHP T cells 7f.117.5 13 3.57 1.98 (Acapatamab)7f.221 14 3.43 2.66 (Acapatamab)7a.1 (UCHT1) 63.4 67.6 3.69 4.31 7a.2 (UCHT1) 56.9 52.4 4.15 4.52 7h.l (OKT3) 15 18.5 2.53 4.95 % TCR- 7h.2 (OKT3) 6.93 6.6 3.32 2.62 (Editing) 7i.l (hOKT3) 16.8 21.5 2.12 2.567i.2 (hOKT3) 8.85 8.84 2.14 3.13 7j.l (FN-18) 8.27 4.61 13.2 6.83 7j.2 (FN-18) 7.18 6.95 48 29.9 7k.1 (SP34-2) 17.8 19 7.09 5.44 7k.2 (SP34-2) 33.1 37.3 14.2 8.25VSVG 12.3 8.22 3.62 3.686IPTS / 200318117.8Attorney Docket No.: AZL-004WOUT 5.66 4.63 3 2.66 7f.1(Acapatamab) 49.6 37.9 2.91 12.7 7f.2(Acapatamab) 49.8 34.7 2.39 5.37 7a.1 (UCHT1) 80.1 78 1.93 2.8 7a.2 (UCHT1) 79.5 73.6 1.59 2.59 7h.l (OKT3) 91.4 91.5 2.69 3.29 %CD25+ 7h.2 (OKT3) 93.3 90.8 2.58 3.61 (Activation) 7i.l (hOKT3) 75.1 48.2 3.17 3.517i.2 (hOKT3) 98.2 97.7 3.75 3.58 7j.l (FN-18) 20.1 18 32.1 22.4 7j.2 (FN-18) 13.1 7.73 18 31.3 7k.1 (SP34-2) 27.5 21.3 3.42 5.56 7k.2 (SP34-2) 79.9 71.5 9.78 20.6 VSVG 17.2 15.2 4.61 2.59UT 4.5 4.94 3.92 2.31Example 5: In vivo assessment of targeted delivery particle co-delivered with AAV expressing CAR in murine tumor model

[0290] Purpose: To assess the cell reprogramming capacity of targeted delivery' particles in vivo, CD3 targeted delivery particles which package CRISPR-Cas9 ribonucleoprotein (RNP) complexes, were dosed with an adeno-associated virus (AAV), which packaged an anti-CD19 CAR-encoding homology-directed repair (HDR) transgene in aNALM6 human PBMC mouse tumor model.

[0291] Methods: On Day 0, NSG-MHC I / II double knock-out (dKO) mice were pre-engrafted with 5xl05luciferase-expressing NALM6 tumor cells via intravenous injection. Three days later (Day 3), human peripheral blood mononuclear cells (PBMCs) were engrafted intravenously. On Day 8, mice were administered PBS or one of two CD3-targeting delivery particles constructs (7a.2 or 7k.2) in combination with AAV encoding a CAR19 HDR transgene that also expressed truncated EGFR (EGFRt). The AAV was administered at a dose of 1 xlO12Delivery particle doses were administered at one of three levels: Low (3.03xl09), Mid (9.09xl09), or High (2.73x 1010). In vivo CAR T cell generation was assessed by measuring EGFRt expression of T cells via flow cytometry, and B cell depletion was evaluated by measuring CD 19+ cells gated from CD45+ cells. These endpoints were measured in mouse blood at Day 12 and Day 14, and in mouse spleen at Day 14.

[0292] Results: Treatment with delivery' particles and AAV resulted in reduced CD19+ target B cell populations (B cell aplasia) and high CAR+ T cells compared to PBS controls. As shown in87IPTS / 200318117.8Attorney Docket No.: AZL-004WOFIG. 16A and FIG. 16B, mice treated with delivery particles and AAV demonstrated B cell aplasia as shown by lower percentages of CD 19+ B cells in the blood at Day 12 and Day 14, respectively. FIG. 16B further shows that the 7a.2 targeting delivery7particles achieved equivalent B cell depletion compared to the 7k.2 across timepoints and doses. Analysis of mouse spleen at Day 14 (FIG. 16C) confirmed that all treatment groups exhibited reduced CD 19+ B cell populations compared to PBS-treated controls. Additionally, as shown in FIG. 16D-FIG.16F, all mice treated with delivery7particles and AAV demonstrated detectable CAR+ T cell populations. CAR+ T cell percentages increased in a dose-dependent manner, with the 7k.2 group showing higher CAR+ T cell populations compared to PBS controls at Day 12 and Day 14 in blood, as well as at Day 14 in spleen tissue. For example, the mid dose of 7k.2 demonstrated an approximate 2-fold increase in CAR+ T cell population percentage compared to the equivalent dose of 7a.2.

[0293] The data indicate that the specific characteristics of various T cell -targeting molecules, such as their differing capacities to activate T cells, can impact editing efficiency in vivo. This may lead to variations in relative editing efficiencies among constructs that differ from those observed in vitro. For instance, 7k-based constructs exhibited higher editing efficiency compared to 7a-based constructs in vivo (see FIG. 16D-F), whereas 7a-based constructs showed superior editing efficiency relativ e to 7k-based constructs in vitro (see FIG. 15).INCORPORATION BY REFERENCE

[0294] All references, articles, publications, patents, patent publications, and patent applications cited herein are incorporated by reference in their entireties for all purposes. However, mention of any reference, article, publication, patent, patent publication, and patent application cited herein is not, and should not be taken as, an acknowledgment or any form of suggestion that they constitute valid prior art or form part of the common general knowledge in any country in the w orld.88IPTS / 200318117.8

Claims

Attorney Docket No.: AZL-004WOCLAIMSWhat is claimed is:

1. A delivery particle comprising:(A) a targeting moiety on the surface of the particle, wherein the targeting moiety comprises one or more antibody or antigen-binding fragments thereof that bind to one or more T cell antigens selected from the group consisting of: CD3, CD5, CD7, CD4, CD28, TCR and CD27; and(B) a payload encapsidated within the particlewherein:(a) the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 86, and a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 87, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 86 and SEQ ID NO: 87, respectively; or(b) the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 72, and a VL chain sequence comprising three light chain CDR sequences, CDR- Ll, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO:

73. optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-LL CDR-L2. and CDR- L3 are according to Kabat, as shown in SEQ ID NO: 72 and SEQ ID NO: 73, respectively; or(c) the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 74, and a VL chain sequence comprising three light chain CDR sequences, CDR- Ll, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 75, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR- L3 are according to Kabat, as shown in SEQ ID NO: 74 and SEQ ID NO: 75, respectively; or89IPTS / 200318117.8Attorney Docket No.: AZL-004WO(d) the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 76, and a VL chain sequence comprising three light chain CDR sequences, CDR- Ll. CDR-L2. and CDR-L3, of the VL sequences set forth in SEQ ID NO:

77. optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR- L3 are according to Kabat, as shown in SEQ ID NO: 76 and SEQ ID NO: 77, respectively; or(e) the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3. of the VH sequences set forth in SEQ ID NO: 78, and a VL chain sequence comprising three light chain CDR sequences, CDR- Ll, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 79, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR- L3 are according to Kabat. as shown in SEQ ID NO: 78 and SEQ ID NO:

79. respectively; or(I) the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 80, and a VL chain sequence comprising three light chain CDR sequences, CDR- Ll. CDR-L2. and CDR-L3, of the VL sequences set forth in SEQ ID NO:

81. optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR- L3 are according to Kabat, as shown in SEQ ID NO: 80 and SEQ ID NO: 81, respectively; or(g) the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3. of the VH sequences set forth in SEQ ID NO: 82, and a VL chain sequence comprising three light chain CDR sequences, CDR- Ll, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 83, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR- L3 are according to Kabat, as shown in SEQ ID NO: 82 and SEQ ID NO: 83, respectively; or(h) the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a VH chain sequence comprising three heavy chain CDR sequences,90IPTS / 200318117.8Attorney Docket No.: AZL-004WOCDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 84, and a VL chain sequence comprising three light chain CDR sequences, CDR- Ll, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 85, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2. and CDR- L3 are according to Kabat. as shown in SEQ ID NO: 84 and SEQ ID NO:

85. respectively; or(i) the antibody or antigen-binding fragment thereof specifically binds CD4 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 88, and a VL chain sequence comprising three light chain CDR sequences, CDR- Ll. CDR-L2. and CDR-L3, of the VL sequences set forth in SEQ ID NO:

89. optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR- L3 are according to Kabat, as shown in SEQ ID NO: 88 and SEQ ID NO: 89, respectively; or(j) the antibody or antigen-binding fragment thereof specifically binds CD28 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3. of the VH sequences set forth in SEQ ID NO: 90, and a VL chain sequence comprising three light chain CDR sequences, CDR- Ll, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 91, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR- L3 are according to Kabat. as shown in SEQ ID NO: 90 and SEQ ID NO:

91. respectively; or(k) the antibody or antigen-binding fragment thereof specifically binds CD28 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 92, and a VL chain sequence comprising three light chain CDR sequences, CDR- Ll. CDR-L2. and CDR-L3, of the VL sequences set forth in SEQ ID NO:

93. optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR- L3 are according to Kabat, as shown in SEQ ID NO: 92 and SEQ ID NO: 93, respectively; or(l) the antibody or antigen-binding fragment thereof specifically binds CD28 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3. of the VH sequences set forth in SEQ ID NO: 94, and a VL chain sequence comprising three light chain CDR sequences, CDR- 91IPTS / 200318117.8Attorney Docket No.: AZL-004WOLI, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 95, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR- L3 are according to Kabat, as shown in SEQ ID NO: 94 and SEQ ID NO: 95, respectively; or(m) the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences. CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 96, and a VL chain sequence comprising three light chain CDR sequences, CDR- Ll, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 97, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2. and CDR- L3 are according to Kabat. as shown in SEQ ID NO: 96 and SEQ ID NO:

97. respectively; or(n) the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 98, and a VL chain sequence comprising three light chain CDR sequences, CDR- Ll. CDR-L2. and CDR-L3, of the VL sequences set forth in SEQ ID NO:

99. optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR- L3 are according to Kabat, as shown in SEQ ID NO: 98 and SEQ ID NO: 99, respectively; or(o) the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3. of the VH sequences set forth in SEQ ID NO: 100, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 101, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat. as shown in SEQ ID NO: 100 and SEQ ID NO: 101, respectively; or(p) the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 100, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1. CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 102, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and 92IPTS / 200318117.8Attorney Docket No.: AZL-004WOCDR-L3 are according to Kabat, as shown in SEQ ID NO: 100 and SEQ ID NO: 102, respectively; or(q) the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 103, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 104, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 103 and SEQ ID NO: 104, respectively; or(r) the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences. CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 105, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 101, optionally wherein CDR-H1, CDR-H2. CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat. as shown in SEQ ID NO: 105 and SEQ ID NO: 101, respectively; or(s) the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 105, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1. CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 102, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 105 and SEQ ID NO: 102, respectively; or(t) the antibody or antigen-binding fragment thereof specifically binds CD7 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3. of the VH sequences set forth in SEQ ID NO: 106, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 107, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat. as shown in SEQ ID NO: 106 and SEQ ID NO: 107, respectively; or93IPTS / 200318117.8Attorney Docket No.: AZL-004WO(u) the antibody or antigen-binding fragment thereof specifically binds CD7 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 108, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1. CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 109, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 108 and SEQ ID NO: 109, respectively; or(v) the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3. of the VH sequences set forth in SEQ ID NO: 110, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 111, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat. as shown in SEQ ID NO: 110 and SEQ ID NO: 111, respectively; or(w) the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 112, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 113, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 112 and SEQ ID NO: 113, respectively; or(x) the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3. of the VH sequences set forth in SEQ ID NO: 114, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 115, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat. as shown in SEQ ID NO: 114 and SEQ ID NO: 115, respectively; or(y) the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences,94IPTS / 200318117.8Attorney Docket No.: AZL-004WOCDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 116, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 117, optionally wherein CDR-H1, CDR-H2. CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat. as shown in SEQ ID NO: 116 and SEQ ID NO: 117, respectively; or(z) the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 118, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 119, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 118 and SEQ ID NO: 119, respectively; or(aa)the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3. of the VH sequences set forth in SEQ ID NO: 120, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 121, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat. as shown in SEQ ID NO: 120 and SEQ ID NO: 121, respectively; or(bb) the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 122, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 123, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 122 and SEQ ID NO: 123, respectively; or(cc)the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3. of the VH sequences set forth in SEQ ID NO: 124, and a VL chain sequence comprising three light chain CDR sequences.95IPTS / 200318117.8Attorney Docket No.: AZL-004WOCDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 125, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 124 and SEQ ID NO: 125, respectively; or(dd) the antibody or antigen-binding fragment thereof specifically binds TCR and comprises a VH chain sequence comprising three heavy chain CDR sequences. CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 126, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 127, optionally wherein CDR-H1, CDR-H2. CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat. as shown in SEQ ID NO: 126 and SEQ ID NO: 127, respectively; or(ee)the antibody or antigen-binding fragment thereof specifically binds TCR and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 128, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1. CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 129, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 128 and SEQ ID NO: 129, respectively; or(ff) the antibody or antigen-binding fragment thereof specifically binds TCR and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3. of the VH sequences set forth in SEQ ID NO: 130, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 129, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat. as shown in SEQ ID NO: 130 and SEQ ID NO: 129, respectively; or(gg) the antibody or antigen-binding fragment thereof specifically binds TCR and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 131, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1. CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 129, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and 96IPTS / 200318117.8Attorney Docket No.: AZL-004WOCDR-L3 are according to Kabat, as shown in SEQ ID NO: 131 and SEQ ID NO: 129, respectively; or(hh) the antibody or antigen-binding fragment thereof specifically binds TCR and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 132, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 133, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 132 and SEQ ID NO: 133, respectively; or(ii) the antibody or antigen-binding fragment thereof specifically binds TCR and comprises a VH chain sequence comprising three heavy chain CDR sequences. CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 134, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 133, optionally wherein CDR-H1, CDR-H2. CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat. as shown in SEQ ID NO: 134 and SEQ ID NO: 133, respectively; or(jj ) the antibody or antigen-binding fragment thereof specifically binds TCR and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 135, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 133, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 135 and SEQ ID NO: 133, respectively.

2. The delivery particle of claim 1, wherein:the antibody or antigen-binding fragment thereof specifically binds CD3 and comprises a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 86, and a variable light (VL) chain sequence comprising three light chain97IPTS / 200318117.8Attorney Docket No.: AZL-004WOCDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 87.

3. The delivery particle of claim 2, wherein:(a) the CDR-H1 comprises the sequence set forth in SEQ ID NO: 136, CDR-H2 comprises the sequence set forth in SEQ ID NO: 137, CDR-H3 comprises the sequence set forth in SEQ ID NO: 138, CDR-L1 comprises the sequence set forth in SEQ ID NO: 139, CDR-L2 comprises the sequence set forth in SEQ ID NO: 140, and CDR-L3 comprises the sequence set forth in SEQ ID NO: 141, according to Kabat or(b) the CDR-H1 comprises the sequence set forth in SEQ ID NO: 142, CDR-H2 comprises the sequence set forth in SEQ ID NO: 143, CDR-H3 comprises the sequence set forth in SEQ ID NO: 144, CDR-L1 comprises the sequence set forth in SEQ ID NO: 145, CDR-L2 comprises the sequence set forth in SEQ ID NO: 146, and CDR-L3 comprises the sequence set forth in SEQ ID NO: 147, according to Chothia; or(c) the CDR-H1 comprises the sequence set forth in SEQ ID NO: 148, CDR-H2 comprises the sequence set forth in SEQ ID NO: 149, CDR-H3 comprises the sequence set forth in SEQ ID NO: 150, CDR-L1 comprises the sequence set forth in SEQ ID NO: 151, CDR-L2 comprises the sequence set forth in SEQ ID NO: 152, and CDR-L3 comprises the sequence set forth in SEQ ID NO: 153, according to IMGT; or(d) the CDR-H1 comprises the sequence set forth in SEQ ID NO: 154, CDR-H2 comprises the sequence set forth in SEQ ID NO: 155, CDR-H3 comprises the sequence set forth in SEQ ID NO: 156, CDR-L1 comprises the sequence set forth in SEQ ID NO: 157, CDR-L2 comprises the sequence set forth in SEQ ID NO: 158, and CDR-L3 comprises the sequence set forth in SEQ ID NO: 159, according to North.

4. The delivery particle of claims 1-3, wherein the antibody or antigen-binding fragment thereof specifically binds CD3 comprising a VH sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 86, and the VL sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 87.98IPTS / 200318117.8Attorney Docket No.: AZL-004WO5. The delivery particle of claims 1-4, wherein the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 86, and the VL sequence set forth in SEQ ID NO: 87.

6. The delivery particle of claims 1-5, wherein the antibody or antigen-binding fragment thereof specifically binds CD3 comprising an scFv at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence set forth in SEQ ID NO: 16 or 15.

7. The delivery particle of claims 1-6, wherein the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the scFv sequence set forth in SEQ ID NO: 16 or 15.

8. A delivery particle comprising:(A) a targeting moiety on the surface of the particle, wherein the targeting moiety comprises one or more antibody or antigen-binding fragments thereof that bind to one or more T cell antigens selected from the group consisting of: CD3, CD5, CD7, CD4, CD28, TCR and CD27; and(B) a payload encapsidated within the particle.

9. The delivery particle of claims 1-8, wherein:(a) the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 86, and the VL sequence set forth in SEQ ID NO: 87; or(b) the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 72, and the VL sequence set forth in SEQ ID NO: 73; or(c) the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 74, and the VL sequence set forth in SEQ ID NO: 75; or(d) the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 76, and the VL sequence set forth in SEQ ID NO: 77; or(e) the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 78, and the VL sequence set forth in SEQ ID NO: 79; or99IPTS / 200318117.8Attorney Docket No.: AZL-004WO(f) the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 80, and the VL sequence set forth in SEQ ID NO: 81; or(g) the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 82, and the VL sequence set forth in SEQ ID NO: 83; or(h) the antibody or antigen-binding fragment thereof specifically binds CD3 comprising the VH sequence set forth in SEQ ID NO: 84, and the VL sequence set forth in SEQ ID NO: 85; or(i) the antibody or antigen-binding fragment thereof specifically binds CD4 comprising the VH sequence set forth in SEQ ID NO: 88, and the VL sequence set forth in SEQ ID NO: 89; or(j) the antibody or antigen-binding fragment thereof specifically binds CD28 comprising the VH sequence set forth in SEQ ID NO: 90, and the VL sequence set forth in SEQ ID NO: 91; or(k) the antibody or antigen-binding fragment thereof specifically binds CD28 comprising the VH sequence set forth in SEQ ID NO: 92, and the VL sequence set forth in SEQ ID NO: 93; or(l) the antibody or antigen-binding fragment thereof specifically binds CD28 comprising the VH sequence set forth in SEQ ID NO: 94, and the VL sequence set forth in SEQ ID NO: 95; or(m) the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence set forth in SEQ ID NO: 96, and the VL sequence set forth in SEQ ID NO: 97; or(n) the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence set forth in SEQ ID NO: 98, and the VL sequence set forth in SEQ ID NO: 99; or(o) the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence set forth in SEQ ID NO: 100, and the VL sequence set forth in SEQ ID NO: 101; or100IPTS / 200318117.8Attorney Docket No.: AZL-004WO(p) the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence set forth in SEQ ID NO: 100, and the VL sequence set forth in SEQ ID NO: 102; or(q) the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence set forth in SEQ ID NO: 103, and the VL sequence set forth in SEQ ID NO: 104; or(r) the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence set forth in SEQ ID NO: 105, and the VL sequence set forth in SEQ ID NO: 101; or(s) the antibody or antigen-binding fragment thereof specifically binds CD5 comprising the VH sequence set forth in SEQ ID NO: 105, and the VL sequence set forth in SEQ ID NO: 102; or(t) the antibody or antigen-binding fragment thereof specifically binds CD7 comprising the VH sequence set forth in SEQ ID NO: 106, and the VL sequence set forth in SEQ ID NO: 107; or(u) the antibody or antigen-binding fragment thereof specifically binds CD7 comprising the VH sequence set forth in SEQ ID NO: 108, and the VL sequence set forth in SEQ ID NO: 109; or(v) the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 110, and the VL sequence set forth in SEQ ID NO: 111; or(w)the antibody or anti gen -binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 112, and the VL sequence set forth in SEQ ID NO: 113; or(x) the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 114, and the VL sequence set forth in SEQ ID NO: 115; or(y) the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 116, and the VL sequence set forth in SEQ ID NO: 117; or101IPTS / 200318117.8Attorney Docket No.: AZL-004WO(z) the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 118, and the VL sequence set forth in SEQ ID NO: 119; or(aa) the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 120, and the VL sequence set forth in SEQ ID NO: 121; or(bb) the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 122, and the VL sequence set forth in SEQ ID NO: 123; or(cc) the antibody or antigen-binding fragment thereof specifically binds CD27 comprising the VH sequence set forth in SEQ ID NO: 124, and the VL sequence set forth in SEQ ID NO: 125; or(dd) the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence set forth in SEQ ID NO: 126, and the VL sequence set forth in SEQ ID NO: 127; or(ee) the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence set forth in SEQ ID NO: 128, and the VL sequence set forth in SEQ ID NO: 129; or(ff) the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence set forth in SEQ ID NO: 130, and the VL sequence set forth in SEQ ID NO: 129; or(gg) the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence set forth in SEQ ID NO: 131, and the VL sequence set forth in SEQ ID NO: 129; or(hh) the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence set forth in SEQ ID NO: 132, and the VL sequence set forth in SEQ ID NO: 133; or(ii) the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence set forth in SEQ ID NO: 134, and the VL sequence set forth in SEQ ID NO: 133; or102IPTS / 200318117.8Attorney Docket No.: AZL-004WO(jj ) the antibody or antigen-binding fragment thereof specifically binds TCR comprising the VH sequence set forth in SEQ ID NO: 135, and the VL sequence set forth in SEQ ID NO: 133.

10. The delivery particle of claims 1-9, wherein:(a) the antibody or antigen-binding fragment thereof specifically binds CD3 comprising an scFv having the sequence set forth in SEQ ID NOs: 16, 15, or 3-14; or (b) the antibody or antigen-binding fragment thereof specifically binds CD5 comprising an scFv having the sequence set forth in SEQ ID NOs: 24-37; or (c) the antibody or antigen-binding fragment thereof specifically binds CD7 comprising an scFv having the sequence set forth in SEQ ID NOs: 38-40; or (d) the antibody or antigen-binding fragment thereof specifically binds CD27 comprising an scFv having the sequence set forth in SEQ ID NOs: 42-57; or (e) the antibody or antigen-binding fragment thereof specifically binds CD4 comprising an scFv having the sequence set forth in SEQ ID NOs: 17-18; or (1) the antibody or antigen-binding fragment thereof specifically binds CD28 comprising an scFv having the sequence set forth in SEQ ID NOs: 19-23; or (g) the antibody or antigen-binding fragment thereof specifically binds TCR comprising an scFv having the sequence set forth in SEQ ID NOs: 58-71.

11. A delivery particle comprising:(a) a targeting moiety on the surface of the particle, wherein the targeting moiety comprises a means for binding a T cell antigen; and(b) a payload encapsidated within the particle.

12. A delivery particle comprising:(a) a targeting moiety on the surface of the particle, wherein the targeting moiety comprises a means for binding a T cell antigen selected from the group consisting of: CD3, CD5, CD7, CD4, CD28, TCR and CD27; and(b) a payload encapsidated within the particle.

13. The particle of any one of claims 1-12. wherein particle further comprises a pseudotyping protein on the surface of the particle, optionally wherein the pseudotyping protein comprises a pseudotyping viral envelope protein further103IPTS / 200318117.8Attorney Docket No.: AZL-004WOoptionally wherein the pseudotyping viral envelope protein is a VSVg protein or variant thereof.

14. The particle of any one of claims 1-13, wherein the particle is a selected from a lipid nanoparticle (LNP) or a virus like particle (VLP).

15. The particle of claim 14, wherein the VLP is a retrovirus-derived particle.

16. The particle of any one of claims 1-15, wherein the payload is selected from a gene editing system, a polynucleotide encoding a transgene, a peptide, and a detectable marker.

17. The particle of claim 16, wherein the gene editing system comprises (i) a fusion protein comprising a Gag polyprotein and a Cas endonuclease, optionally wherein the Cas endonuclease is fused to the C-terminus of the Gag polyprotein: and (ii) a guide RNA.

18. A virus like particle (VLP) comprising(a) a targeting moiety on the surface of the particle, wherein the targeting moiety comprises an antibody or an antigen-binding fragment thereof that binds to a T cell antigen selected from CD5, CD7, and CD27;(b) a pseudotyping viral envelope protein;(c) a gene-editing system encapsidated within the VLP; and(d) a polynucleotide encoding a transgene.

19. The VLP of claim 18, wherein(a) the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 96, and a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 97, optionally wherein CDR-H1, CDR-H2, CDR-H3. CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 96 and SEQ ID NO: 97, respectively: or(b) the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 98,104IPTS / 200318117.8Attorney Docket No.: AZL-004WOand a VL chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 99, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 98 and SEQ ID NO: 99, respectively: or(c ) the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 100, and a VL chain sequence comprising three light chain CDR sequences, CDR-Ll, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 101, optionally wherein CDR-HL CDR-H2, CDR-H3, CDR-L1, CDR-L2. and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 100 and SEQ ID NO: 101, respectively; or(d) the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 100, and a VL chain sequence comprising three light chain CDR sequences, CDR-Ll, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 102, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 100 and SEQ ID NO: 102, respectively; or(e) the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences. CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 103, and a VL chain sequence comprising three light chain CDR sequences, CDR-Ll, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 104, optionally wherein CDR-HL CDR-H2, CDR-H3, CDR-L1, CDR-L2. and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 103 and SEQ ID NO: 104, respectively; or(f) the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heav chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 105, and a VL chain sequence comprising three light chain CDR sequences, CDR-Ll, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 101,105IPTS / 200318117.8Attorney Docket No.: AZL-004WOoptionally wherein CDR-HL CDR-H2, CDR-H3, CDR-LL CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 105 and SEQ ID NO: 101, respectively; or(g) the antibody or antigen-binding fragment thereof specifically binds CD5 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1. CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 105, and a VL chain sequence comprising three light chain CDR sequences, CDR-Ll, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 102, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 105 and SEQ ID NO: 102, respectively; or(h) the antibody or antigen-binding fragment thereof specifically binds CD7 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 106, and a VL chain sequence comprising three light chain CDR sequences, CDR-Ll, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 107, optionally wherein CDR-HL CDR-H2, CDR-H3, CDR-L1, CDR-L2. and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 106 and SEQ ID NO: 107, respectively; or(i) the antibody or antigen-binding fragment thereof specifically binds CD7 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 108, and a VL chain sequence comprising three light chain CDR sequences, CDR-Ll, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 109, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as show n in SEQ ID NO: 108 and SEQ ID NO: 109, respectively; or(j) the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences. CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 110, and a VL chain sequence comprising three light chain CDR sequences, CDR-Ll, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 111, optionally wherein CDR-HL CDR-H2, CDR-H3, CDR-L1, CDR-L2. and CDR-L3106IPTS / 200318117.8Attorney Docket No.: AZL-004WOare according to Kabat, as shown in SEQ ID NO: 110 and SEQ ID NO: 111, respectively; or(k) the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 112, and a VL chain sequence comprising three light chain CDR sequences, CDR-Ll, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 113, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 112 and SEQ ID NO: 113, respectively; or(l) the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-HL CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 114, and a VL chain sequence comprising three light chain CDR sequences, CDR-Ll, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 115, optionally wherein CDR-HL CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat. as shown in SEQ ID NO: 114 and SEQ ID NO: 115, respectively; or(l) the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 116, and a VL chain sequence comprising three light chain CDR sequences, CDR-Ll, CDR-L2. and CDR-L3, of the VL sequences set forth in SEQ ID NO: 117, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 116 and SEQ ID NO: 117, respectively; or(m) the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-HL CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 118, and a VL chain sequence comprising three light chain CDR sequences, CDR-Ll, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 119, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat. as shown in SEQ ID NO: 118 and SEQ ID NO: 119, respectively; or107IPTS / 200318117.8Attorney Docket No.: AZL-004WO(n) the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 120, and a VL chain sequence comprising three light chain CDR sequences, CDR- Ll, CDR-L2. and CDR-L3, of the VL sequences set forth in SEQ ID NO: 121, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 120 and SEQ ID NO: 121, respectively; or(o) the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1. CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 122, and a VL chain sequence comprising three light chain CDR sequences, CDR- Ll, CDR-L2, and CDR-L3, of the VL sequences set forth in SEQ ID NO: 123, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat. as shown in SEQ ID NO: 122 and SEQ ID NO: 123, respectively; or(p) the antibody or antigen-binding fragment thereof specifically binds CD27 and comprises a VH chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, of the VH sequences set forth in SEQ ID NO: 124, and a VL chain sequence comprising three light chain CDR sequences, CDR- Ll, CDR-L2. and CDR-L3, of the VL sequences set forth in SEQ ID NO: 125, optionally wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are according to Kabat, as shown in SEQ ID NO: 124 and SEQ ID NO: 125, respectively.

20. A virus like particle (VLP) comprising(a) a targeting moiety on the surface of the particle, wherein the targeting moiety comprises a means for binding to a T cell antigen selected from CD5, CD7, and CD27;(b) a pseudotyping viral envelope protein;(c) a gene-editing system encapsidated within the VLP; and(d) a polynucleotide encoding a transgene.108IPTS / 200318117.8Attorney Docket No.: AZL-004WO21. A method of delivering a payload to a population of target cells comprising contacting the population of target cells with the particle of any one of the preceding claims,wherein the population of target cells expresses a T cell antigen selected from CD5, CD7, and CD27.

22. The method of claim 21, wherein the delivery efficiency of the particle is greater than 20%, greater than 30%, greater than 40%, or greater than 50%.

23. The method of claim 21, wherein the delivery efficiency of the particle is at least 5% higher than the delivery efficiency of a particle comprising one or more targeting moieties that bind to CD4, CD3, and / or CD28.

24. A method of editing a population of target cells comprising contacting the population of target cells with the particle of any one of the preceding claims,wherein the population of target cells expresses a T cell antigen selected from CD5, CD7, and CD27.

25. The method of claim 24, wherein the editing efficiency of the particle is greater than 20%, greater than 30%, greater than 40%, or greater than 50%.

26. The method of claim 24, wherein the editing efficiency of the particle is at least 5% higher than the editing efficiency of a particle comprising one or more targeting moieties that bind to CD4, CD3, and / or CD28.

27. A method of modifying a population of target cells to express a transgene comprising contacting the population of target cells with the particle of any one of the preceding claims,wherein the population of target cells expresses a T cell antigen selected from CD5, CD7, and CD27.

28. The method of claim 27, wherein the integration efficiency of the particle is at least 7%.

29. The method of claim 27, wherein the integration efficiency of the particle is at least 2% higher than the integration efficiency of a particle comprising one or more targeting moieties that bind to CD4, CD3, and / or CD28.

30. A method of delivering a payload to a population of target cells comprising contacting the population of target cells with a particle comprising:109IPTS / 200318117.8Attorney Docket No.: AZL-004WO(a) a targeting moiety on the surface of the particle, comprising means for binding human CD5; and(b) a payload encapsidated within the particle,wherein the delivery efficiency of the particle is at least 5% higher than the deliver}' efficiency a particle comprising one or more targeting moieties that bind to CD4, CD3, and / or CD28.

31. A method of delivering a payload to a population of target cells comprising contacting the population of target cells with a particle comprising:(a) a targeting moiety' on the surface of the particle, comprising means for binding human CD7; and(b) a payload encapsidated within the particle,wherein the delivery' efficiency of the particle is at least 5% higher than the delivery' efficiency a particle comprising one or more targeting moieties that bind to CD4, CD3, and / or CD28.

32. A method of delivering a pay load to a population of target cells comprising contacting the population of target cells with a particle comprising:(a) a targeting moiety on the surface of the particle, comprising means for binding human CD27; and(b) a payload encapsidated within the particle,wherein the delivery efficiency of the particle is at least 5% higher than the delivery’ efficiency a particle comprising one or more targeting moieties that bind to CD4, CD3, and / or CD28.110IPTS / 200318117.8

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