Chimeric antigen receptors and uses thereof

Abstract

Aspects of the disclosure relate to chimeric antigen receptors (CARs) comprising an antigen binding domain (e.g., anti-TSHR), transmembrane domain (e.g., CD28), and a cytoplasmic domain (e.g., CD27, CD-137, etc.) and a safety mechanism comprising an inducible apoptosis trigger. In some aspects, the disclosure relates to use of the CARs in T cells, compositions, kits and methods for the treatment of thyroid cancers.

1 - 14 . (canceled) 
     
     
         15 . A method of treating a subject having cancer, the method comprising: administering to the subject an immune cell comprising a chimeric antigen receptor (CAR) comprising:
 a single chain variable fragment (scFv) specific for thyroid specific hormone receptor (TSHR), wherein the scFv comprises the following complementarity determining regions (CDRs): NYWMN (SEQ ID NO: 11), RIDPSDSETHYNQNFKD (SEQ ID NO: 12), SGY, KSSQSLLDSDGKTYLN (SEQ ID NO: 14), LVSKVDS (SEQ ID NO: 15), and WQGTHSPLT (SEQ ID NO: 16);   a transmembrane domain;   a cytoplasmic domain containing one or more of a CD28 signaling domain, a CD137 intracellular domain, a CD27 domain, a CD3zeta signal transduction domain; and   a cytoplasmic domain that contains an inducible trigger of apoptosis.   
     
     
         16 . The method of  claim 15 , wherein the cancer is thyroid cancer. 
     
     
         17 . The method of  claim 16 , wherein the thyroid cancer is differentiated thyroid cancer. 
     
     
         18 . The method of  claim 17 , wherein the thyroid cancer is papillary thyroid cancer. 
     
     
         19 . The method of  claim 17 , wherein the thyroid cancer is follicular thyroid cancer. 
     
     
         20 . The method of  claim 15 , wherein the inducible trigger of apoptosis is iCasp9. 
     
     
         21 . The method of  claim 15 , wherein the inducible trigger of apoptosis is iCasp9. 
     
     
         22 . The method of  claim 15 , wherein the transmembrane domain is a CD28 or CD8 transmembrane domain. 
     
     
         23 . The method of  claim 15 , wherein the cytoplasmic domain contains two or more of a CD27 signaling domain, a CD137, and a CD3zeta signal transduction domain. 
     
     
         24 . The method of  claim 15 , wherein the immune cell is a T cell or NK cell. 
     
     
         25 . The method of  claim 15 , wherein the immune cell is a T cell. 
     
     
         26 . The method of  claim 15 , wherein the subject is a human.