Plectin-1 binding antibodies and uses thereof

Abstract

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 .- 112 . (canceled) 
     
     
         113 . 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 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.   
     
     
         114 . The method of  claim 113 , wherein the antibody or antigen binding fragment thereof is a monoclonal antibody, a Fab fragment, a Fab′ fragment, a F(ab′)2 fragment, an affibody, a dsFv diabody, a scFv, or a Fv fragment. 
     
     
         115 . The method of  claim 113 , wherein the antibody or antigen binding fragment thereof is coupled to a targeted agent. 
     
     
         116 . The method of  claim 115 , wherein the targeted agent is a detectable moiety or a therapeutic agent. 
     
     
         117 . The method of  claim 116 , wherein the therapeutic agent is a cytotoxic moiety or an immunomodulatory moiety. 
     
     
         118 . The method of  claim 113 , where in the cancer is selected from the group consisting of pancreatic cancer, ovarian cancer, esophageal cancer, prostate cancer, lung cancer, and head and neck squamous cell carcinoma. 
     
     
         119 . A method for targeting an agent to a cancer cell in a subject, the method comprising administering to the subject a composition comprising a targeted agent and 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.   
     
     
         120 . The method of  claim 119 , wherein the targeted agent is a detectable moiety or a therapeutic agent. 
     
     
         121 . The method of  claim 120 , wherein the therapeutic agent is a cytotoxic moiety or an immunomodulatory moiety. 
     
     
         122 . The method of  claim 120 , wherein the detectable moiety is selected from the group consisting of a radioactive isotope, a magnetic compound, an x-ray absorber, a chemical compound, a biological tag, and a fluorescent molecule. 
     
     
         123 . The method of  claim 119 , wherein the antibody or antigen binding fragment thereof is a monoclonal antibody, a Fab fragment, a Fab′ fragment, a F(ab′)2 fragment, an affibody, a dsFv diabody, a scFv, or a Fv fragment. 
     
     
         124 . A method for detecting a cancer cell, the method comprising contacting a cancer cell with 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.   
     
     
         125 . The method of  claim 124 , wherein the antibody or antigen binding fragment thereof binds to plectin-1 on the surface of the cancer cell in a subject. 
     
     
         126 . The method of  claim 124 , wherein the antibody or antigen binding fragment thereof is a monoclonal antibody, a Fab fragment, a Fab′ fragment, a F(ab′)2 fragment, an affibody, a dsFv diabody, a scFv, or a Fv fragment. 
     
     
         127 . The method of  claim 124 , wherein the antibody or antigen binding fragment thereof is coupled to a detectable moiety. 
     
     
         128 . The method of  claim 127 , wherein the detectable moiety is selected from the group consisting of a radioactive isotope, a magnetic compound, an x-ray absorber, a chemical compound, a biological tag, and a fluorescent molecule.