Glypican-3-specific antibody and uses thereof

Abstract

The present invention relates to compositions and methods for diagnosing and treating diseases, disorders or conditions associated with dysregulated expression of GPC3. The invention provides novel antibodies that specifically bind to glypican-3 (GPC3). The invention also relates to a fully human chimeric antigen receptor (CAR) wherein the CAR is able to target GPC3.

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         14 . An isolated chimeric antigen receptor (CAR) comprising a human GPC3 binding domain and a CD3 zeta signaling domain. 
     
     
         15 . The isolated CAR of  claim 14 , further comprising the sequence of a co-stimulatory signaling domain. 
     
     
         16 . The isolated CAR of  claim 15 , wherein the co-stimulatory signaling domain is selected from the group consisting of the CD28 signaling domain, the 4-1BB signaling domain, and any combination thereof. 
     
     
         17 . The isolated CAR of  claim 14 , wherein the human GPC3 binding domain is a human antibody or a fragment thereof is selected from the group consisting of an Fab fragment, an F(ab′) 2  fragment, an Fv fragment, and a single chain Fv (scFv). 
     
     
         18 . The isolated CAR of  claim 15 , wherein the antibody or a fragment thereof comprises a heavy chain and light chain, wherein the amino acid sequence of the heavy chain is selected from the group consisting of SEQ ID NOs: 12-16 and the amino acid sequence of the light chain is selected from the group consisting of SEQ ID NOs: 17-21. 
     
     
         19 . A method of providing an anti-tumor immunity in a mammal, the method comprising administering to the mammal an effective amount of a genetically modified cell comprising an isolated nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the isolated nucleic acid sequence comprises the sequence of a human GPC3 binding domain and the nucleic acid sequence of a CD3 zeta signaling domain. 
     
     
         20 . The method of  claim 19 , wherein the cell is an autologous T cell. 
     
     
         21 . The method of  claim 19 , wherein the mammal is a human. 
     
     
         22 . A method of treating a mammal having a disease, disorder or condition associated with dysregulated expression of mesothelin, the method comprising administering to the mammal an effective amount of a genetically modified cell comprising an isolated nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the isolated nucleic acid sequence comprises the sequence of a human GPC3 binding domain and the nucleic acid sequence of a CD3 zeta signaling domain. 
     
     
         23 . The method of  claim 22 , wherein the disease, disorder or condition associated with dysregulated expression of GPC3 is selected from the group consisting of liver cancer, pancreatic cancer, ovarian cancer, stomach cancer, lung cancer, endometrial cancer, hepatocellular carcinoma, and any combination thereof.