CHIMERIC ANTIGEN RECEPTORS AND METHODS OF USE THEREOF
The present invention provides chimeric antigen receptors, cells expressing same and methods of using same for treatment various disorders such as cancer.
1 . A chimeric antigen receptor (CAR) comprising an intracellular signaling domain, a transmembrane domain and an extracellular domain
2 . The CAR of claim 1 , wherein the transmembrane domain further comprises a stalk region positioned between the extracellular domain and the transmembrane domain.
3 . The CAR or claim 1 , wherein the transmembrane domain comprises CD28.
4 . The CAR of claim 1 , further comprising one or more additional costimulatory molecules positioned between the transmembrane domain and the intracellular signaling domain
5 . The CAR of claim 4 , wherein the costimulatory molecules is CD28, 4-1BB, ICOS, or OX40.
6 . The CAR of claim 1 , wherein the intracellular signaling domain comprises a CD3 zeta chain.
7 . The CAR of claim 1 , wherein the extracellular domain is an antibody.
8 . The CAR of claim 7 , wherein the antibody is a Fab or a scFV.
9 . The CAR of claim 7 , wherein the antibody is specific for BCMA, CD138, CCR4, PD-1, PDL-1, PD-L2, CXCR4, GITR, SARS virus, flavivirus, MERS virus, influenza virus, or CAIX.
10 . A nucleic acid encoding the CAR of any one of the preceding claims further comprising a nucleic acid encoding a polypeptide positioned after the intracellular signaling domain.
11 . The nucleic acid of claim 10 , wherein the polypeptide is an antibody
12 . The nucleic acid of claim 11 , wherein the antibody is a scFV.
13 . The nucleic acid of claim 12 , wherein the antibody is specific for BCMA, CD138, CCR4, PD-1, PDL-1, PD-L2, CXCR4, GITR, SARS virus, flavivirus, MERS virus, influenza virus, or CAIX
14 . A vector comprising the nucleic acid of claim 11 .
15 . A cell comprising the vector of claim 14 .
16 . A genetically engineered cell which express and bear on the cell surface membrane the chimeric antigen receptor of claim 1 .
17 . The genetically engineered cell of claim 16 , wherein the cell is a T-cell or an NK cell.
18 . The genetically engineered cell of claim 17 , wherein the T cell is CD4 + or CD8 + .
19 . The genetically engineered cell of claim 18 , which comprises a mixed population of CD4 + and CD8 cells + .
20 . The cell of claim 16 , wherein the cell is further engineered to express and secrete a polypeptide
21 . The cell of claim 20 , wherein the expressed and secreted polypeptide is anti-PDL-1.