Glypican-3 antibody and uses thereof
AssigneesThe Trustees of the University of Pennsylvania, The United States of America as represented by the Department of Veterans Affairs
InventorDavid Kaplan
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Abstract
The present invention relates to compositions and methods of isolated polynucleotides that encode or polypeptides comprising glypican-3 (GPC3). The invention also includes a chimeric antigen receptor (CAR) wherein the CAR is able to target GPC3. The invention further includes methods of treating a subject or diagnosing and treating diseases, disorders or conditions associated with dysregulated glypican-3.
Claims23
An isolated polynucleotide encoding an anti-glypican-3 (GPC3) antibody or antigen-binding fragment thereof comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises SEQ ID NO:
- 1 and the light chain variable region comprises SEQ ID NO:
- 3.
An isolated anti-GPC3 antibody or antigen-binding fragment thereof comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises SEQ ID NO:
- 2 and the light chain variable region comprises SEQ ID NO:
- 4.
A method of imaging or visualizing a sample taken from a normal or malignant tissue, the method comprising contacting the sample with a labeled anti-GPC3 antibody or antigen-binding fragment thereof, wherein the anti-GPC3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises SEQ ID NO:
- 2 and the light chain variable region comprises SEQ ID NO:
- 4.
A method of inhibiting growth of a GPC3-expressing tumor cell, the method comprising contacting the tumor cell with an anti-GPC3 antibody or an antigen-binding fragment thereof comprising a heavy chain variable region and a light chain variable region, wherein an amino acid sequence of the heavy chain variable region comprises SEQ ID NO:
- 2 and the amino acid sequence of the light chain variable region comprises SEQ ID NO:
- 4.
An isolated nucleic acid sequence encoding a chimeric antigen receptor (CAR) comprising a glypican-3 (GPC3) binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain, wherein the isolated nucleic acid sequence that encodes the GPC3 binding domain comprises SEQ ID NO:
- 1 and SEQ ID NO:
- 3.
An isolated chimeric antigen receptor (CAR) comprising a GPC3 binding domain and a CD3 zeta signaling domain, wherein the GPC3 binding domain comprises SEQ ID NO:
- 2 and SEQ ID NO:
- 4.
A method of providing an anti-tumor immunity in a subject with a tumor that expresses glypican-3 (GPC3), the method comprising administering to the subject an effective amount of a genetically modified T cell comprising an isolated nucleic acid sequence encoding a chimeric antigen receptor (CAR) that comprises a glypican-3 (GPC3) binding domain, a 4-1BB co-stimulatory signaling domain, and a CD3 zeta signaling domain, wherein the GPC3 binding domain comprises SEQ ID NO:
- 2 and SEQ ID NO:
- 4.
A method of treating a glypican-3 (GPC3)-expressing liver cancer in a subject, the method comprising administering to the subject an effective amount of a genetically modified T cell comprising an isolated nucleic acid sequence encoding a chimeric antigen receptor (CAR) that comprises a GPC3 binding domain, a 4-1BB co-stimulatory signaling domain, and a CD3 zeta signaling domain, wherein the GPC3 binding domain comprises SEQ ID NO:
- 2 and SEQ ID NO:
- 4.
Dependencies are inferred from the claim text.