Use of chimeric antigen receptor modified cells to treat cancer
The present disclosure relates to compositions and methods for compositions, methods, and kits for treating cancer using chimeric antigen receptor (CAR) modified cells. Some embodiments of the present disclosure relate to an isolated nucleic acid sequence encoding CAR. The CAR may include an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain. The antigen binding domain may bind to an antigen of a non-essential organ.
1. An isolated nucleic acid encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an extracellular domain, a transmembrane domain, and an intracellular domain, wherein the extracellular domain binds to Guanylate cyclase 2C (GUCY2C), and wherein the CAR comprises amino acid sequence SEQ ID NO: 40.
2. The isolated nucleic acid of claim 1 , wherein the GUCY2C comprises amino acid sequence SEQ ID NO: 33.
3. The isolated nucleic acid of claim 1 , wherein the intracellular domain comprises a costimulatory signaling region that comprises an intracellular domain of a costimulatory molecule selected from the group consisting of CD27, CD28, 4-1BB, OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, and any combination thereof.
4. The isolated nucleic acid of claim 1 , wherein the intracellular domain comprises a CD3 zeta signaling domain.
5. A vector comprising the isolated nucleic acid of claim 1 .
6. An isolated cell comprising the isolated nucleic acid of claim 1 .
7. A composition comprising a population of T cells comprising the CAR of claim 1 .
8. A pharmaceutical composition comprising a population of T cells comprising the CAR of claim 1 .
9. A method of stimulating a T cell response, the method comprising contacting cells expressing GUCY2C with an effective amount of the pharmaceutical composition of claim 8 , thereby stimulating a T cell response.
10. The method of claim 9 , wherein the cells expressing GUCY2C are in a subject.
11. The method of claim 10 , wherein the subject is diagnosed with colorectal cancer.
12. A method of stimulating an immune response in a population of cells expressing GUCY2C, the method comprising contacting the population of cells with an effective amount of the pharmaceutical composition of claim 8 .
13. The method of claim 12 , wherein the immune response is a T cell-mediated immune response.
14. The method of claim 12 , wherein the population of cells expressing GUCY2C are in a subject.
15. The method of claim 12 , where the immune response is an anti-tumor immune response.