Chimeric antigen receptor comprising interleukin-15 intracellular domain and uses thereof

Abstract

Provided herein are chimeric antigen receptors (CARs) comprising an antigen binding domain (e.g., CD19, CD30, GD2, etc.), transmembrane domain (e.g., CD28), and a cytoplasmic domain (e.g., CD27, 4-1BB, etc.). In some aspects, the disclosure relates to use of the CARs in T cells, compositions, kits and methods.

1 - 63 . (canceled) 
     
     
         64 . A monospecific chimeric antigen receptor (CAR) comprising:
 an antigen binding domain that is monospecific for CD19;   a transmembrane domain, wherein the transmembrane domain comprises a CD28 transmembrane domain; and   a cytoplasmic domain comprising a 4-1BB intracellular domain, a CD27 intracellular domain, a CD3zeta signal transduction domain, and an inducible caspase 9 domain.   
     
     
         65 . The monospecific CAR of  claim 64 , wherein the antigen binding domain is a single-chain variable fragment (scFv). 
     
     
         66 . The monospecific CAR of  claim 64 , where the antigen binding domain comprises the amino acid sequences set forth in SEQ ID NOs: 11 and 12. 
     
     
         67 . The monospecific CAR of  claim 64 , wherein the CD28 transmembrane domain comprises the amino acid sequence set forth in SEQ ID NO: 23, 24, or 25. 
     
     
         68 . The monospecific CAR of  claim 64 , where the 4-1BB intracellular domain comprises the amino acid sequence set forth in SEQ ID NO: 42. 
     
     
         69 . The monospecific CAR of  claim 64 , wherein the CD27 intracellular domain comprises the amino acid sequence set forth in SEQ ID NO: 38. 
     
     
         70 . The monospecific CAR of  claim 64 , wherein the CD3zeta signal transduction domain comprises the amino acid sequence set forth in SEQ ID NO: 39 or 40. 
     
     
         71 . The monospecific CAR of  claim 64 , wherein the inducible caspase 9 (iCasp9) domain comprises the amino acid sequence set forth in SEQ ID NO: 28 or 29. 
     
     
         72 . The monospecific CAR of  claim 71 , further comprising an FKBP binding protein comprising the amino acid sequence set forth in SEQ ID NO: 30. 
     
     
         73 . An immune cell comprising the monospecific CAR of  claim 64 , wherein the immune cell is a T cell or NK cell. 
     
     
         74 . A composition comprising a plurality of the immune cell of  claim 73 . 
     
     
         75 . A method comprising administering the immune cell of  claim 73  to a subject having cancer. 
     
     
         76 . The method of  claim 75 , wherein the subject is a human. 
     
     
         77 . The method of  claim 75 , wherein the cancer is leukemia. 
     
     
         78 . The method of  claim 77 , wherein the leukemia is B cell leukemia.