Anti-LFL2 Antibodies for the Diagnosis, Prognosis and Treatment of Cancer

Abstract

Particular anti-LFL2 antibody compositions are provided herein. These antibodies may be used for diagnosis, prognosis, therapeutic monitoring and treatment of cancer, especially breast cancer, head/neck cancer, lung cancer, ovarian cancer, stomach cancer and pancreatic cancer. Furthermore, anti-LFL2 antibodies are provided herein which target the LFL2 stump remaining after proteolytic cleavage of the extracellular domain of LFL2. Additionally, anti-LFL2 antibodies are provided herein which target the stroma surrounding cancer tumors, wherein said stroma-targeting anti-LFL2 antibodies disrupt the integrity of the stroma surrounding the cancer tumor, and also make the stroma more permeable to chemotherapeutic agents and other molecular drug agents that target tumor cells.

1 . A method for inhibiting the growth of a solid tumor comprising contacting the tumor-associated stoma with an antibody that specifically binds to LFL2 SEQ ID NO: 1 or SEQ ID NO: 6, wherein the antibody is selected from the group consisting of: an antibody having a heavy chain variable region amino acid sequence of SEQ ID NO: 3 and a light chain variable region amino acid sequence of SEQ ID NO: 5, an antibody produced by the hybridoma cell line deposited as ATCC Accession No. PTA-6163, an antibody produced by the hybridoma cell line deposited as ATCC Accession No. PTA-6256, and an antibody produced by the hybridoma cell line deposited as ATCC Accession No. PTA-6330. 
     
     
         2 . The method of  claim 1 , wherein the solid tumor is selected from the group consisting of breast, lung, ovarian, colon and pancreatic tumors. 
     
     
         3 . The method of  claim 1 , wherein the antibody is conjugated to a cytotoxic agent. 
     
     
         4 . The method of  claim 3 , wherein the cytotoxic agent is auristatin E or auristatin F. 
     
     
         5 . A method for inhibiting the growth of a solid tumor comprising contacting the tumor-associated stoma with a chemotherapeutic agent and an antibody that specifically binds to LFL2 SEQ ID NO: 1 or SEQ ID NO: 6, wherein the antibody is selected from the group consisting of: an antibody having a heavy chain variable region amino acid sequence of SEQ ID NO: 3 and a light chain variable region amino acid sequence of SEQ ID NO: 5, an antibody produced by the hybridoma cell line deposited as ATCC Accession No. PTA-6163, an antibody produced by the hybridoma cell line deposited as ATCC Accession No. PTA-6256, and an antibody produced by the hybridoma cell line deposited as ATCC Accession No. PTA-6330. 
     
     
         6 . The method of  claim 5 , wherein the solid tumor is selected from the group consisting of breast, lung, ovarian, colon and pancreatic tumors. 
     
     
         7 . The method of  claim 5 , wherein the antibody is conjugated to a cytotoxic agent. 
     
     
         8 . The method of  claim 7 , wherein the cytotoxic agent is auristatin E or auristatin F. 
     
     
         9 . A method for inhibiting the growth of a solid tumor comprising administering a pharmaceutical composition comprising an antibody that specifically binds to LFL2 SEQ ID NO: 1 or SEQ ID NO: 6 in tumor-associated stroma, wherein the antibody is selected from the group consisting of: an antibody having a heavy chain variable region amino acid sequence of SEQ ID NO: 3 and a light chain variable region amino acid sequence of SEQ ID NO: 5, an antibody produced by the hybridoma cell line deposited as ATCC Accession No. PTA-6163, an antibody produced by the hybridoma cell line deposited as ATCC Accession No. PTA-6256, and an antibody produced by the hybridoma cell line deposited as ATCC Accession No. PTA-6330. 
     
     
         10 . The method of  claim 9 , wherein the solid tumor is selected from the group consisting of breast, lung, ovarian, colon and pancreatic tumors. 
     
     
         11 . The method of  claim 9 , wherein the pharmaceutical composition further comprises a chemotherapeutic agent. 
     
     
         12 . The method of  claim 9 , wherein the antibody is conjugated to a cytotoxic agent. 
     
     
         13 . The method of  claim 12 , wherein the cytotoxic agent is auristatin E or auristatin F.