Antibodies Specific to Sonic Hedgehog and Method of Use Thereof
AssigneeThe Regents of the University of California
InventorsDavid M. Jablons, Bhairavi Tolani, Biao He, Etienne Giroux-Leprieur
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Abstract
Antibodies that specifically bind to a Sonic Hedgehog (Shh) polypeptide, or an antigen binding fragment thereof, are provided. Also provided are methods of treating an individual for cancer using the Shh polypeptide antibodies. Methods of analyzing a tissue sample for cell-surface expression of a full-length Shh polypeptide are also provided.
Claims96
An antibody, or an antigen binding fragment thereof, that specifically binds a Sonic Hedgehog (Shh) polypeptide comprising:
- a heavy chain variable (VH) region comprising:
- a complementarity determining region (CDRH1) comprising the amino acid sequence:
- SYTMS (SEQ ID NO:10);
- a CDRH2 comprising the amino acid sequence:
- TISSGGGNTYYPDSVKG (SEQ ID NO:11);
- and
- a CDRH3 comprising the amino acid sequence:
- DYRSLFAY (SEQ ID NO:12);
- and
- a light chain variable (VL) region comprising:
- a CDRL1 comprising the amino acid sequence:
- SASSSVSYMH (SEQ ID NO:13);
- a CDRL2 comprising the amino acid sequence:
- STSNLAS (SEQ ID NO:14);
- and
- a CDRL3 comprising the amino acid sequence:
- QQRSSYPFT (SEQ ID NO:15).
An antibody conjugate comprising an antibody, or an antigen binding fragment thereof, comprising an immunoglobulin (Ig) polypeptide attached to a therapeutic agent, wherein the antibody specifically binds to full-length Shh polypeptide expressed on a cell surface.
The method of any one of claims 35 to 52, wherein the individual has or is suspected of having pancreatic, colon, gastric, lung, breast, prostate or blood cancer.
A method of analyzing a tissue sample, comprising:
- contacting cells of a tissue sample with a first detectable binding agent that specifically binds to a Shh polypeptide, under conditions sufficient for the first detectable binding agent to preferentially bind full-length Shh polypeptide expressed on a cell surface;
- and
- measuring an amount of the first detectable binding agent bound to the cells, wherein the measured amount indicates a level of full-length Shh polypeptide expressed on the cell surface.
A method of diagnosing a cancer in an individual, comprising:
- contacting cells of a tumor tissue sample from an individual having or suspected of having a cancer with a first detectable binding agent that specifically binds to a Shh polypeptide, under conditions sufficient for the first detectable binding agent to preferentially bind full-length Shh polypeptide expressed on a cell surface;
- measuring an amount of the first detectable binding agent bound to the cells, wherein the measured amount indicates a level of full-length Shh polypeptide expressed on the cell surface;
- and
- diagnosing the cancer based on the measured amount.
A method of immunizing an individual, comprising administering to an individual an antigenic peptide comprising a fragment of a C-terminal Shh polypeptide, in a manner sufficient to elicit an adaptive immune response against a cell of the individual, wherein the cell expresses full-length Shh polypeptide on a cell surface.
Dependencies are inferred from the claim text.