Mutant CTLA4 gene transfected T cell and composition including same for anticancer immunotherapy
A transformed T-cell for T-cell therapy, and a composition including the same for anticancer immunotherapy. More particularly, the transformed T-cell is characterized by the transfection of a gene for coding a chimera protein. The T-cell, to which the gene for coding the chimera protein is transected, may improve the therapeutic effects induced by immune tolerance of cancer cells, and furthermore maximize anti-cancer effects by activating signal transduction to induce the activation of T-cells. Also, the disclosure allows treatments that minimize side effects such as the development of autoimmune diseases due to systematic T-cell activation.
1. An isolated nucleic acid encoding a fusion protein, said fusion protein comprising:
(i)a T-cell surface tolerance-inducing receptor lacking its intracellular signaling domain; and
(ii)an intracellular signaling domain of the CD28 protein, wherein the fusion protein had the amino acid sequence set fourth in SEQ ID NO: 5 or 7.
2. The isolated nucleic acid of claim 1 , further comprising an extracellular domain and transmembrane domain, wherein both domains are from the CTLA4 protein and are encoded by the nucleic acid set forth in SEQ ID NO: 9.
3. The isolated nucleic acid of claim 1 , wherein the intracellular domain of the CD28 protein is encoded by the nucleic acid sequence set forth by SEQ ID NO: 10.
4. A viral vector comprising the nucleic acid of claim 1 .
5. The viral or carrier of claim 4 , wherein the viral carrier is any one selected from the group consisting of retrovirus, lentivirus, adenovirus, and adeno-associated virus.
6. An isolated T-cell transduced with the viral vector of claim 4 .
7. The isolated T-cell of claim 6 , wherein the T-cell is a cancer antigen-specific CD4 T-cell, a cancer antigen-specific CD8 T-cell, or a combination of a cancer antigen-specific CD4 T-cell and a cancer antigen-specific CD8 T-cell.
8. The isolated T-cell of claim 6 , wherein the T-cell is a cancer antigen-specific T-cell.
9. The isolated T-cell of claim 8 , wherein the cancer antigen-specific T-cell is any one selected from the group consisting of a T-cell isolated from the cancer tissue of a patient, a T-cell transduced with a receptor gene that recognizes cancer antigen, and a T-cell transduced with chimeric antigen receptor (CAR) gene.
10. The isolated T-cell of claim 8 , wherein the cancer antigen is any one selected from the group consisting of MUC1, CD19, HER2, EGFR, CD20, CEA, PSMA, GD2, folate receptor, IL-13Ra2, Lewis-Y antigen, NY-ESO-1, MART-1, gp100, tyrosinase, tyrosinase-related proteins, MAGE, and WT-1.
11. A pharmaceutical composition for treating cancer, comprising the transduced T-cell of claim 6 .
12. The pharmaceutical composition of claim 11 , wherein the transduced T-cell comprises a cancer antigen-specific CD4 T-cell, a cancer antigen-specific CD8 T-cell, or a combination of a cancer antigen-specific CD4 T-cell and a cancer antigen-specific CD8 T-cell.
13. An in vitro method for producing the transduced T-cell of claim 6 , the method comprising transducing an isolated T-cell with the viral carrier of claim 4 .