Mutant CTLA4 gene transfected T cell and composition including same for anticancer immunotherapy

Patent metadata

Field	Value
Publication number	US-9688740-B2
Application number	US-201214354562-A
Country	US
Kind code	B2
Filing date	Oct 26, 2012
Priority date	Oct 26, 2011
Publication date	Jun 27, 2017
Grant date	Jun 27, 2017

Abstract

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.

First claim

The invention claimed is:

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 .

Assignees

• Nat Cancer Ct

Inventors

• Choi Kyungho
• Shin Jaehun
• Lee Sang-Jin

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• C07K14/70521 Primary

  CD28, CD152 · CPC title

• C12N15/62

  DNA sequences coding for fusion proteins · CPC title

• C07K19/00 Primary

  Hybrid peptides {, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes} · CPC title