Chimeric antigen receptors targeting GPC3 and uses thereof

1. A nucleic acid encoding a chimeric antigen receptor targeting glypican-3 (GPC3) for expressing at a surface of a human T lymphocyte, wherein the chimeric antigen receptor targeting GPC3 comprises, connected in an order of, an extracellular binding domain, a transmembrane region, and an intracellular signaling domain, wherein the extracellular binding domain comprises a single chain antibody scFv(GPC3) which specifically recognizes a C-terminal epitope of GPC3, and wherein the chimeric antigen receptor comprises SEQ ID NO: 25.

2. The nucleic acid according to claim 1 comprising SEQ ID NO: 21.

3. A vector comprising a nucleic acid encoding a chimeric antigen receptor targeting glypican-3 (GPC3) for expressing at a surface of a human T lymphocyte, wherein the chimeric antigen receptor targeting GPC3 comprises, connected in an order of, an extracellular binding domain, a transmembrane region, and an intracellular signaling domain, wherein the extracellular binding domain comprises a single chain antibody scFv(GPC3) which specifically recognizes a C-terminal epitope of GPC3, and wherein the chimeric antigen receptor comprises SEQ ID NO: 25.

4. The vector according to claim 3 , wherein the vector comprises SEQ ID NO: 30.

5. A virus comprising a vector including nucleic acid encoding a chimeric antigen receptor targeting glypican-3 (GPC3) for expressing at a surface of a human T lymphocyte, wherein the chimeric antigen receptor targeting GPC3 comprises, connected in an order of, an extracellular binding domain, a transmembrane region, and an intracellular signaling domain, wherein the extracellular binding domain comprises a single chain antibody scFv(GPC3) which specifically recognizes a C-terminal epitope of GPC3, and wherein the chimeric antigen receptor comprises SEQ ID NO: 25.

6. A genetically modified T lymphocyte transfected with a nucleic acid encoding a chimeric antigen receptor targeting glypican-3 (GPC3) for expressing at a surface of a human T lymphocyte, wherein the chimeric antigen receptor targeting GPC3 comprises, connected in an order of, an extracellular binding domain, a transmembrane region, and an intracellular signaling domain, wherein the extracellular binding domain comprises a single chain antibody scFv(GPC3) which specifically recognizes a C-terminal epitope of GPC3, and wherein the chimeric antigen receptor comprises SEQ ID NO: 25.

7. A genetically modified T lymphocyte comprising a chimeric antigen receptor expressed at a surface thereof, wherein the chimeric antigen receptor is encoded by a nucleic acid comprising SEQ ID NO: 21.

8. A genetically modified T lymphocyte comprising a chimeric antigen receptor expressed at a surface thereof, wherein the chimeric antigen receptor comprises SEQ ID NO: 25.

9. A genetically modified T lymphocyte transfected with a vector comprising a nucleic acid encoding a chimeric antigen receptor targeting glypican-3 (GPC3) for expressing at a surface of a human T lymphocyte, wherein the chimeric antigen receptor targeting GPC3 comprises, connected in an order of, an extracellular binding domain, a transmembrane region, and an intracellular signaling domain, wherein the extracellular binding domain comprises a single chain antibody scFv(GPC3) which specifically recognizes a C-terminal epitope of GPC3, and wherein the chimeric antigen receptor comprises SEQ ID NO: 25.

10. A genetically modified T lymphocyte transfected with a virus comprising a vector comprising nucleic acid encoding a chimeric antigen receptor targeting glypican-3 (GPC3) for expressing at a surface of a human T lymphocyte, wherein the chimeric antigen receptor targeting GPC3 comprises, connected in an order of, an extracellular binding domain, a transmembrane region, and an intracellular signaling domain, wherein the extracellular binding domain comprises a single chain antibody scFv(GPC3) which specifically recognizes a C-terminal epitope of GPC3, wherein the chimeric antigen receptor comprises SEQ ID NO: 25.

11. A method of treating a hepatocellular carcinoma comprising administering to a human in need thereof an effective amount of genetically modified lymphocytes comprising a chimeric antigen receptor (CAR) that targets glypican-3 (GPC3), wherein the CAR comprises an extracellular binding domain, transmembrane region, and intracellular signaling domain, wherein the CAR binds a C-terminal epitope of GPC3, wherein the chimeric antigen receptor comprises SEQ ID NO: 25, and wherein the amount of the genetically modified lymphocytes is effective in reducing tumor volume after the administration.

12. The method of claim 11 , further comprising administering cyclophosphamide to the human.

13. The method of claim 11 , wherein the genetically modified lymphocytes are infused into the human.

14. The method of claim 11 , wherein the genetically modified lymphocytes comprise a cytotoxic T cell (CTL).

15. The method of claim 11 , wherein the CAR is encoded by SEQ ID NO: 21.

16. The method of claim 11 , wherein the C-terminal epitope of GPC3 comprises amino acids 524-563 of GPC3.

17. The method of claim 11 , wherein the amount of the genetically modified lymphocytes is effective in reducing tumor volume by at least 50%.

18. The method of claim 11 , wherein the human comprises viable CD4+ or CD8+ T cells in peripheral blood after the administration.

19. The method of claim 11 , wherein the amount of the genetically modified lymphocytes is effective in increasing survival time of the human after the administration.