Plectin-1 binding antibodies and uses thereof
Aspects of the disclosure provide compositions and methods for treating cancer characterized by surface expression of plectin-1. In some embodiments, the disclosure provides anti-plectin-1 antibodies. In some embodiments, the anti-plectin-1 antibodies are conjugated to a targeted moiety (e.g., a therapeutic moiety or a detectable label).
1. An antibody or antigen binding fragment thereof that specifically binds to a cell-surface exposed plectin-1 antigen, wherein the antibody or antigen binding fragment thereof comprises
a heavy chain variable region having a sequence set forth as: SEQ ID NO: 24 and a light chain variable region having a sequence set forth as: SEQ ID NO: 46; or
a heavy chain variable region having a sequence set forth as: SEQ ID NO: 68 and a light chain variable region having a sequence set forth as: SEQ ID NO: 90.
2. The antibody of claim 1 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region having a sequence set forth as: SEQ ID NO: 24 and a light chain variable region having a sequence set forth as: SEQ ID NO: 46.
3. The antibody of claim 1 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region having a sequence set forth as: SEQ ID NO: 68 and a light chain variable region having a sequence set forth as: SEQ ID NO: 90.
4. The antibody of claim 1 , wherein the antibody is coupled to a targeted agent.
5. An antibody, or antigen binding fragment thereof, that specifically binds to cell-surface exposed plectin-1 antigen, and that comprises six complementarity determining regions (CDRs): CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3,
wherein CDRH1 comprises a sequence as set forth in SEQ ID NO: 18, CDRH2 comprises a sequence as set forth in SEQ ID NO: 20, CDRH3 comprises a sequence as set forth in SEQ ID NO:22, CDRL1 comprises a sequence as set forth in SEQ ID NO: 40, CDRL2 comprises a sequence as set forth in SEQ ID NO: 42, and CDRL3 comprises a sequence as set forth in SEQ ID NO: 44; or
wherein CDRH1 comprises a sequence as set forth in SEQ ID NO: 62, CDRH2 comprises a sequence as set forth in SEQ ID NO: 64, CDRH3 comprises a sequence as set forth in SEQ ID NO: 66, CDRL1 comprises a sequence as set forth in SEQ ID NO: 84, CDRL2 comprises a sequence as set forth in SEQ ID NO: 86, and CDRL3 comprises a sequence as set forth in SEQ ID NO: 88.
6. The antibody or antigen binding fragment thereof of claim 5 , wherein the antibody or antigen binding fragment thereof comprises
a heavy chain variable region having a sequence with at least 85% identity to SEQ ID NO: 24 and a light chain variable region with at least 85% identity to SEQ ID NO: 46; or
a heavy chain variable region having a sequence with at least 85% identity to SEQ ID NO: 68 and a light chain variable region with at least 85% identity to SEQ ID NO: 90.
7. The antibody or antigen binding fragment thereof of claim 5 , wherein the antibody or antigen binding fragment thereof is coupled to a targeted agent.
8. A composition comprising the antibody or antigen binding fragment thereof of claim 5 , optionally further comprising a pharmaceutically acceptable excipient.
9. A method for treating cancer, the method comprising administering to a subject having cancer an effective amount of an antibody or antigen binding fragment thereof of claim 1 , wherein the cancer is characterized by surface expression of plectin-1 and is selected from the group consisting of pancreatic cancer, ovarian cancer, esophageal cancer, prostate cancer, lung cancer, and head and neck squamous cell carcinoma.
10. A method for detecting a cancer cell, the method comprising contacting a cancer cell in vitro with the antibody or antigen binding fragment thereof of claim 5 .