Anti-CD20 antibodies and CAR-T structures
Anti-CD20 antibodies (e.g., UniAbs™) and CAR-T structures are disclosed, along with methods of making such antibodies and CAR-T structures, compositions, including pharmaceutical compositions, comprising such antibodies and CAR-T structures, and their use to treat disorders that are characterized by the expression of CD20.
1 . A chimeric antigen receptor (CAR) T-cell comprising a CAR comprising an extracellular antigen-binding domain that binds to CD20, comprising a heavy chain variable region sequence comprising: a CDR1 sequence comprising SEQ ID NO: 4, a CDR2 sequence comprising SEQ ID NO: 5, and a CDR3 sequence comprising SEQ ID NO: 6; wherein the CDR1, CDR2, and CDR3 sequences are present in a human VH framework.
2 . The CAR-T cell of claim 1 , comprising a heavy chain variable region sequence comprising at least 95% sequence identity to SEQ ID NO: 8.
3 . The CAR T-cell of claim 2 , comprising a heavy chain variable region sequence comprising SEQ ID NO: 8.
4 . A CAR-T cell comprising a CAR comprising an extracellular antigen-binding domain that binds to CD20, comprising a heavy chain variable region sequence comprising SEQ ID NO: 8.
5 . A pharmaceutical composition comprising the CAR-T cell of claim 1 .
6 . A pharmaceutical composition comprising the CAR-T cell of claim 4 .
7 . A kit for treating a disease or disorder in an individual in need, wherein the kit comprises:
(a) the pharmaceutical composition of claim 5 ; and
(b) instructions for use.
8 . The kit of claim 7 , further comprising at least one additional reagent.
9 . The kit of claim 8 , wherein the at least one additional reagent comprises a chemotherapeutic drug.
10 . A kit for treating a disease or disorder in an individual in need, wherein the kit comprises:
(a) the pharmaceutical composition of claim 6 ; and
(b) instructions for use.
11 . The kit of claim 10 , further comprising at least one additional reagent.
12 . The kit of claim 11 , wherein the at least one additional reagent comprises a chemotherapeutic drug.
13 . A method for the treatment of a disorder characterized by expression of CD20, comprising administering to a subject with said disorder a CAR-T cell according to claim 1 .
14 . The method of claim 13 , wherein the disorder is a hematological malignancy.
15 . The method of claim 13 , wherein the disorder is non-Hodgkin lymphoma (NHL).
16 . The method of claim 13 , wherein the disorder is chronic lymphocytic leukemia (CLL).
17 . The method of claim 13 , wherein the disorder is follicular lymphoma (FL).
18 . The method of claim 13 , wherein the disorder is diffuse large B-cell lymphoma (DLBCL).
19 . The method of claim 13 , wherein the disorder is mantle cell lymphoma (MCL).
20 . The method of claim 13 , wherein the disorder is acute lymphocytic leukemia (ALL).
21 . The method of claim 13 , wherein the disorder is marginal zone lymphoma (MZL).
22 . A method for the treatment of a disorder characterized by expression of CD20, comprising administering to a subject with said disorder a CAR-T cell according to claim 4 .
23 . The method of claim 22 , wherein the disorder is a hematological malignancy.
24 . The method of claim 22 , wherein the disorder is non-Hodgkin lymphoma (NHL).
25 . The method of claim 22 , wherein the disorder is chronic lymphocytic leukemia (CLL).
26 . The method of claim 22 , wherein the disorder is follicular lymphoma (FL).
27 . The method of claim 22 , wherein the disorder is diffuse large B-cell lymphoma (DLBCL).
28 . The method of claim 22 , wherein the disorder is mantle cell lymphoma (MCL).
29 . The method of claim 22 , wherein the disorder is acute lymphocytic leukemia (ALL).
30 . The method of claim 22 , wherein the wherein the disorder is marginal zone lymphoma (MZL).