Chimeric antigen receptor-expressing t cells as anti-cancer therapeutics

Abstract

Cytotoxic lymphocytes expressing chimeric antigen receptors (CAR) that target and bind small conjugate molecules (SCM) are disclosed, as well as methods of using the cells and the SCMs in the treatment of cancer.

1 . A two component cancer therapeutic comprising:
 (a) a small conjugate molecule (SCM) comprising a targeted moiety conjugated to a tumor receptor ligand via a linker, wherein the tumor receptor ligand is folate, the targeted moiety is fluorescein isothiocyanate (FITC), and the linker is ethylenediamine; and   (b) a chimeric antigen receptor (CAR)-expressing cytotoxic lymphocyte, wherein the CAR is a fusion protein comprising a recognition region, a co-stimulation domain and an activation signaling domain, and wherein the CAR has binding specificity for the targeted moiety or can be bound by the targeted moiety.   
     
     
         2 .- 7 . (canceled) 
     
     
         8 . The two component cancer therapeutic of  claim 1 , wherein the recognition region of the CAR is a single chain fragment variable (scFv) region of an anti-FITC antibody. 
     
     
         9 . The two component cancer therapeutic of  claim 1 , wherein the co-stimulation domain of the CAR is chosen from CD28, CD 137 (4-1BB), and CD 134 (OX40). 
     
     
         10 . The two component cancer therapeutic of  claim 1 , wherein the activation signaling domain of the CAR is a T cell CD3ζ chain. 
     
     
         11 . The two component cancer therapeutic of  claim 1 , wherein the recognition region is a single chain fragment variable (scFv) region of an anti-FITC antibody, wherein the co-stimulation domain is CD137 (4-1BB), and wherein the activation signaling domain is a T cell CD3ζ chain. 
     
     
         12 .- 48 . (canceled) 
     
     
         49 . A two component cancer therapeutic comprising:
 (a) a small conjugate molecule (SCM) comprising a targeted moiety conjugated to a tumor receptor ligand via a linker, wherein the targeted moiety is fluorescein isothiocyanate (FITC), the tumor receptor ligand is folate, and the linker is ethylenediamine and;   (b) a chimeric antigen receptor (CAR)-expressing cytotoxic lymphocyte, wherein the CAR is a fusion protein comprising a recognition region, a co-stimulation domain and an activation signaling domain, and wherein the recognition region is a single chain fragment variable (scFv) region of an anti-FITC antibody, the co-stimulation domain is CD137 (4-1BB), and the activation signaling domain is a T cell CD3ζ chain; and wherein the CAR has binding specificity for the targeted moiety or can be bound by the targeted moiety.