COSTIMULATORY CHIMERIC ANTIGEN RECEPTOR T CELLS TARGETING IL13R-alpha-2

Abstract

Chimeric transmembrane immunoreceptors (CAR) which include an extracellular domain that includes IL-13 or a variant thereof that binds interleukin-13Rα2 (IL13Rα2), a transmembrane region, a costimulatory domain and an intracellular signaling domain are described.

What is claimed is: 
     
         1 . A population of human T cells transduced by a vector comprising an expression cassette encoding a chimeric antigen receptor, wherein chimeric antigen receptor comprises:
 a human IL-13 variant comprising the amino acid sequence of SEQ ID NO: 3 with up to 5 single amino acid substitutions, provided that the amino acid at position 11 of SEQ ID NO: 3 other than E;   a transmembrane domain selected from: a CD4 transmembrane domain or variant thereof having 1-5 amino acid substations, a CD8 transmembrane domain or variant thereof having 1-5 amino acid substitutions, a CD28 transmembrane domain or a variant thereof having 1-5 amino acid substations, and a CD3 transmembrane domain or a variant thereof having 1-5 amino acid substitutions;   a costimulatory domain selected from the group consisting of: a CD28 costimulatory domain or a variant thereof having 1-5 amino acid substitutions, a 4IBB costimulatory domain or a variant thereof having 1-5 amino acid substitutions and an OX40 costimulatory domain or a variant thereof having 1-5 amino acid substitutions;   and CD3 ζ signaling domain of a variant thereof having 1-5 amino acid substitutions.   
     
     
         2 . The population of human T cells of  claim 1 , wherein the chimeric antigen receptor comprising an amino acid sequence selected from SEQ ID NOs: 10, 31-48 and 52. 
     
     
         3 . The population of human T cells of  claim 1 , wherein the chimeric antigen receptor comprises SEQ ID NO: 10. 
     
     
         4 . A composition comprising T cells harboring a nucleic acid molecule comprising a nucleotide sequence encoding a chimeric antigen receptor molecule comprising the amino acid sequence of SEQ ID NO: 10. 
     
     
         5 . A composition of comprising T cells harboring an expression vector comprising a nucleotide sequence encoding a chimeric antigen receptor molecule comprising the amino acid sequence of SEQ ID NO: 10. 
     
     
         6 . The composition of  claim 5 , wherein the expression vector is a lentiviral vector. 
     
     
         7 . The composition of  claim 4 , wherein the nucleic acid molecule further comprises a nucleotide sequence encoding a GMSCFRa signal sequence preceding the nucleotide sequence encoding the chimeric antigen receptor. 
     
     
         8 . The composition of  claim 7 , wherein the GMSCFRa signal sequence comprises the amino acid sequence of SEQ ID NO:2. 
     
     
         9 . The composition of  claim 4 , wherein the nucleic acid molecule further comprises a nucleotide sequence encoding a T2A ribosome skip sequence following the nucleotide sequence encoding the chimeric antigen receptor. 
     
     
         10 . The composition of  claim 9 , wherein T2A ribosome skip sequence comprises the amino acid sequence of SEQ ID NO:8. 
     
     
         11 . The composition of  claim 9 , wherein the nucleic acid molecule further comprises a nucleotide sequence encoding a truncated CD19 following the nucleotide sequence encoding the T2A ribosome skip sequence. 
     
     
         12 . The composition of  claim 10 , wherein the truncated CD19 comprises the amino acid sequence of SEQ ID NO:9. 
     
     
         13 . The composition of  claim 5 , wherein the T cells comprise central memory T cells.