Glypican-3 Antibody And Uses Thereof
AssigneeThe Trustees of the University of Pennsylvania
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.
Claims31
An isolated polynucleotide encoding an anti-glypican-3 (GPC3) antibody or fragment thereof comprising a heavy chain and a light chain, wherein the isolated polynucleotide encoding the heavy chain comprises SEQ ID NO:
- 1 and the isolated polynucleotide encoding the light chain comprises SEQ ID NO:
- 3.
An isolated polypeptide for an anti-GPC3 antibody or fragment thereof comprising a heavy chain and a light chain, wherein the isolated polypeptide of the heavy chain comprises SEQ ID NO:
- 2 and the isolated polypeptide of the light chain comprises SEQ ID NO:
- 4.
An isolated anti-GPC3 antibody or fragment thereof comprising a heavy chain and a light chain, wherein the isolated polypeptide specifically binds to SEQ ID NO:17.
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 fragment thereof, wherein the anti-GPC3 antibody or fragment thereof comprises a heavy chain and a light chain, wherein the heavy chain comprises SEQ ID NO:
- 2 and the light chain comprises SEQ ID NO:
- 4.
A method for diagnosing a condition associated with expression of GPC3 in a cell, the method comprising:
- a) contacting the cell with an anti-GPC3 antibody fragment comprising a heavy chain and a light chain, wherein the heavy chain comprises SEQ ID NO:
- 2 and the light chain comprises SEQ ID NO:
- 4;
- and
- b) detecting GPC3 expression, wherein the expression of GPC3 indicates a likelihood of a condition associated with the expression of GPC3.
A method of diagnosing, prognosing, or determining risk of liver cancer in a subject, the method comprising:
- contacting the sample derived from the subject with an anti-GPC3 antibody fragment comprising a heavy chain and a light chain, wherein an amino acid sequence of the heavy chain comprises SEQ ID NO:
- 2 and the amino acid sequence of the light chain comprises SEQ ID NO:
- 4;
- and
- detecting GPC3 in the sample, wherein the detection of GPC3 indicates a likelihood of liver cancer in the subject.
A method of inhibiting growth of a GPC3-expressing tumor cell, the method comprising contacting the tumor cell with an anti-GPC3 antibody or a fragment thereof comprising a heavy chain and a light chain, wherein an amino acid sequence of the heavy chain comprises SEQ ID NO:
- 2 and the amino acid sequence of the light chain 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, the method comprising administering to the subject an effective amount of a genetically modified cell comprising an isolated nucleic acid sequence encoding a chimeric antigen receptor (CAR) that comprises a glypican-3 (GPC3) binding domain and a CD3 zeta signaling domain, wherein the GPC3 binding domain comprises a heavy chain comprising SEQ ID NO:
- 2 and a light chain comprising SEQ ID NO:
- 4.
A method of treating a subject having a disease, disorder or condition associated with dysregulated expression of glypican-3, the method comprising administering to the subject an effective amount of a genetically modified cell comprising an isolated nucleic acid sequence encoding a chimeric antigen receptor (CAR) that comprises 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.
Dependencies are inferred from the claim text.