Antibodies that bind cell surface GRP78
AssigneeUniversity of Southern California
InventorsParkash Gill, Ren Liu, Amy Lee
Life of this patent
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Abstract
This application provides, inter alia, antibodies or antigen-binding fragments thereof, targeting cell surface GRP78 expressed on tumor cells, tumor endothelial cells, and tumor initiating cancer cells. These anti-GRP78 antibodies, or antigen-binding fragments thereof, have a high affinity for GRP78 and are less immunogenic compared to their unmodified parent antibodies in a given species, e.g., a human, and function to inhibit GRP78. Importantly, these isolated novel antibodies and antigen-binding fragments thereof, attenuate PI3K signaling and promote apoptosis in tumor cells, while leaving normal cells unaffected. The antibodies and antigen-binding fragments are useful for UPR-targeted cancer therapeutic treatments.
Claims7
An isolated antibody or antigen-binding fragment thereof that binds to human cell surface glucose regulated protein 78 (GRP78)(SEQ ID NO:
- 1), wherein said antibody or antigen-binding fragment binds to an epitope depicted in SEQ ID NO:
- 31 comprises a heavy chain variable region and a light chain variable region selected from the group consisting of the following pairs of sequences:
- SEQ ID NO:
- 13 and SEQ ID NO:
- 23;
- SEQ ID NO:
- 15 and SEQ ID NO:
- 27;
- SEQ ID NO:
- 17 and SEQ ID NO:
- 25;
- SEQ ID NO:
- 19 and SEQ ID NO:
- 25;
- SEQ ID NO:
- 19 and SEQ ID NO:
- 29;
- or SEQ ID NO:
- 21 and SEQ ID NO:
- 23.
Dependencies are inferred from the claim text.