Chimeric antigen receptors targeting GPC3 and uses thereof

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.

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.

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.

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.

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.

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.

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.

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.