Car based immunotherapy
The disclosure provides chimeric antigen receptors (CARs), T cells comprising such CARs, nucleic acids that encode such CARS, and methods of use thereof, e.g., to treat cancer such as B cell malignancies.
1. A chimeric antigen receptor (CAR) comprising an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain, wherein the costimulatory signaling region consists essentially of a CD28 signaling domain, a CD137 signaling domain and a CD27 signaling domain, wherein the antigen binding domain is an scFv, wherein the CAR further comprises a 2A peptide linker and an iCasp9 domain, and wherein the CAR is arranged as follows:
scFv-CD28-CD137-CD27-CD3z-2A-iCasp9.
2. The CAR of claim 1 , wherein the antigen binding domain binds to a tumor antigen, wherein the tumor antigen is selected from the group consisting of CD19, CD20, CD22, ROR1, mesothelin, CD33/IL3Ra, c-Met, PSMA, Glycolipid F77, EGFRvIII, GD-2, NY-ESO-1 TCR, and MAGE A3 TCR, or any combination thereof.
3. The CAR of claim 2 , wherein the tumor antigen is CD19.
4. An isolated nucleic acid encoding the chimeric antigen receptor (CAR) of claim 1 .
5. The isolated nucleic acid of claim 1 , wherein the sequence is codon-optimized for expression in human cells.
6. A vector comprising the isolated nucleic acid of claim 1 .
7. A cell comprising the chimeric antigen receptor (CAR) of claim 1 .
8. The cell of claim 7 , wherein the cell is selected from the group consisting of a T cell, a Natural Killer (NK) cell, a cytotoxic T lymphocyte (CTL), and a regulatory T cell.