Cell/gene therapies targeting MAGE-A4 peptide
The present disclosure relates to compositions and methods for treating a subject having cancer associated with melanoma-associated antigen 4 (MAGE-A4) peptide. The disclosure includes the embodiments relate to a chimeric antigen receptor (CAR) that binds MAGE-A4 peptide, a polynucleotide encoding a CAR that binds the MAGE-A4 peptide, a modified cell comprising a CAR that binds the MAGE-A4 peptide, and a population of modified cells comprising a CAR that binds the MAGE-A4 peptide.
1 . A chimeric antigen receptor (CAR), wherein the CAR comprises an extracellular domain, a transmembrane domain, and an intracellular domain, wherein the extracellular domain comprises amino acid sequence SEQ ID NO: 10 or 13, and wherein the intracellular domain comprises a CD3 zeta signaling domain and a co-stimulatory signaling domain comprising an intracellular domain of CD28 or 4-1 BB.
2 . The CAR of claim 1 , wherein the CAR binds a human melanoma-associated antigen 4 (MAGE-A4) peptide.
3 . The CAR of claim 1 , wherein the CAR binds a MAGE-A4 peptide comprising amino acid sequence SED ID NO: 14.
4 . The CAR of claim 1 , wherein the CAR comprises amino acid sequence SED ID NO: 11 or 12.
5 . The CAR of claim 1 , wherein the CAR comprises amino acid sequence SED ID NO: 16, or 17.
6 . A composition comprising the CAR of claim 1 and a carrier.
7 . A pharmaceutical composition comprising the CAR of claim 1 and a pharmaceutically acceptable carrier.
8 . A nucleic acid encoding the CAR of claim 1 .
9 . A vector comprising a nucleic acid encoding the CAR of claim 8 .
10 . A cell comprising a nucleic acid encoding the CAR of claim 1 .
11 . A population of cells comprising a nucleic acid encoding the CAR of claim 1 .
12 . The population of cells of claim 11 , wherein the population of cells comprises T cells and/or NK cells.
13 . A pharmaceutical composition comprising the population of T cells of claim 12 .
14 . A method of stimulating an anti-tumor immune response in a human subject in need thereof, the method comprising administering an effective amount of the pharmaceutical composition of claim 13 to the human subject, thereby stimulating an anti-tumor immune response.
15 . The method of claim 14 , wherein the human subject is diagnosed with lung cancer, colon cancer, or bladder cancer.
16 . A method of stimulating an immune response in a population of cells expressing MAGE-A4 peptide, the method comprising contacting the population of cells with an effective amount of the pharmaceutical composition of claim 13 .
17 . The method of claim 16 , wherein the immune response is a T cell-mediated immune response.
18 . The method of claim 16 , wherein the population of cells is in a human subject.
19 . The method of claim 16 , wherein the immune response is an anti-tumor immune response.
20 . The CAR of claim 1 , wherein the transmembrane domain comprises a transmembrane domain of CD8a or CD28.