Chimeric antigen receptors targeting cd37

Abstract

Described herein are chimeric antigen receptors (CARs) targeting CD37, as well as related molecules and methods.

1 .- 35 . (canceled) 
     
     
         36 . A method of treating a CD37+ cancer in a subject, the method comprising administering a Chimeric Antigen Receptor (CAR)-T cell to the subject, the CAR-T cell comprising a CAR polypeptide, the CAR polypeptide comprising:
 a) an extracellular domain comprising a CD37-binding sequence;   b) a transmembrane domain; and   c) a T cell intracellular signaling domain.   
     
     
         37 . The method of  claim 36 , wherein the CD37+ cancer is a B-cell malignancy. 
     
     
         38 . The method of  claim 36 , wherein the subject has cancer relapse after anti-CD19 and/or anti-CD20 therapy, or the subject is refractory to anti-CD19 and/or anti-CD20 therapy. 
     
     
         39 . The method of  claim 36 , wherein the CD37+ cancer is a lymphoma or a leukemia. 
     
     
         40 . The method of  claim 39 , wherein the lymphoma is B-cell Non-Hodgkin Lymphoma (NHL), mantle cell lymphoma, Burkitt's lymphoma, B-cell lymphoblastic lymphoma, diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), marginal zone lymphoma, or T-cell lymphoma. 
     
     
         41 . The method of  claim 39 , wherein the lymphoma is Burkitt's lymphoma. 
     
     
         42 . The method of  claim 39 , wherein the lymphoma is mantle cell lymphoma. 
     
     
         43 . The method of  claim 39 , wherein the lymphoma is T-cell lymphoma. 
     
     
         44 . The method of  claim 43 , wherein the T-cell lymphoma is Peripheral T Cell Lymphoma (PTCL). 
     
     
         45 . The method of  claim 39 , wherein the leukemia is acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphocytic leukemia (ALL), B-cell lymphoblastic leukemia, or chronic lymphocytic leukemia (CLL). 
     
     
         46 . The method of  claim 39 , wherein the leukemia is chronic lymphocytic leukemia. 
     
     
         47 . The method of  claim 39 , wherein the leukemia is B-cell lymphoblastic leukemia. 
     
     
         48 . The method of  claim 39 , wherein the leukemia is acute myeloid leukemia. 
     
     
         49 . The method of  claim 36 , wherein the extracellular domain comprises an antibody reagent. 
     
     
         50 . The method of  claim 49 , wherein the antibody reagent comprises an antibody light chain variable domain of SEQ ID NO: 4 and an antibody heavy chain variable domain of SEQ ID NO: 2. 
     
     
         51 . The method of  claim 36 , wherein the transmembrane domain comprises the transmembrane domain from CD8, 4-1BB or CD28. 
     
     
         52 . The method of  claim 36 , wherein the transmembrane domain comprises the transmembrane domain from CD8. 
     
     
         53 . The method of  claim 36 , wherein the transmembrane domain comprises the transmembrane domain from CD28. 
     
     
         54 . The method of  claim 36 , wherein the T cell intracellular domain comprises a CD3-zeta intracellular signaling domain. 
     
     
         55 . The method of  claim 36 , wherein the CAR polypeptide further comprises a 4-1BB co-stimulatory domain. 
     
     
         56 . The method of  claim 36 , wherein the subject is a human subject. 
     
     
         57 . The method of  claim 36 , wherein the CAR polypeptide comprises a sequence selected from SEQ ID NO: 9 or 15.