Therapeutic and diagnostic anti-hsp70 antibodies

Abstract

Methods and compositions for the detection, prevention and treatment of infectious diseases, primary and metastatic neoplastic diseases, including, but not limited to human sarcomas and carcinomas are described. In particular, specific antibodies are provided, which are capable of binding an epitope of Hsp70 that is extracellularly localized on diseased tissue and cells, in particular on tumor cells and infected cells.

1 . A method of treating a tumor or modulating the immune response in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an antibody or antigen-binding fragment thereof that binds to an extracellular localized epitope of Hsp70 on tumor cells. 
     
     
         2 . The method of  claim 1 , wherein said tumor is a human tumor selected from the group consisting of colon, lung, stomach, prancreas, head and neck, ovary, and/or breast cancer, melanoma, glioblastoma, sarcoma and or leukemia such as AML, ALL, MDS or blastocytoma. 
     
     
         3 . The method of  claim 1 , wherein said epitope comprises or consist of the amino acid sequence NLLGRFEL (SEQ ID NO: 1) or TKDNNLLGRFELSG (SEQ ID NO: 2). 
     
     
         4 . The method of  claim 1 , wherein the antibody is a monoclonal antibody. 
     
     
         5 . The method of  claim 4 , wherein the antibody is monoclonal antibody cmHsp70.1 as produced by hybridoma cmHsp70.1, deposited with the DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, Mascheroder Weg 1b, D-38124 Braunschweig, Germany on Nov. 14, 2003, and assigned Accession Number DSM ACC2629, or cmHsp70.2 as produced by hybridoma cmHsp70.2, deposited with the DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH on Nov. 14, 2003, and assigned Accession Number DSM ACC2630. 
     
     
         6 . The method of  claim 1 , wherein the antibody or antigen-binding fragment competes with an antibody of  claim 5  for binding to an extracellular localized epitope of Hsp70 on human tumor cells. 
     
     
         7 . The method of  claim 1 , wherein the antibody or antigen-binding fragment is capable of exhibiting an inhibitory effect on the cytolytic activity of NK cells against Hsp70 expressing tumor cells. 
     
     
         8 . The method of  claim 1 , wherein the antibody is a human, humanized, xenogeneic, or a chimeric human-murine antibody. 
     
     
         9 . The method of  claim 1 , wherein the antigen-binding fragment is selected from the group consisting of a single chain Fv fragment, an F(ab′) fragment, an F(ab) fragment, and an F(ab′) 2  fragment. 
     
     
         10 . The method of  claim 1 , wherein the antibody is designed to be administered intravenously, intramuscularly, subcutaneously, intraperitoneally, or as an aerosol. 
     
     
         11 . The method of  claim 1 , wherein said tumor is selected from the group consisting of carcinomas of lung, colorectum, pancreas, larynx, stomach, head, neck, breast, ovaries, uterine cervix, liver, peripheral and central nervous system, sarcomas, chronic myeloic leukemia (CML), acute myeloic leukemia (AML), acute lymphatic leukemia (ALL), non Hodgkin Lymphoma (NHL), myeloproliferative syndrome (MPS), myelodysplastic syndrome (MDS), plasmocytoma, melanoma and metastatic tumors. 
     
     
         12 . The method of  claim 1 , wherein said disorder related to an immune response relates to a viral infection, bacterial infection, rheumatoid arthritis, lupus erythematodes, asthma bronchiale. 
     
     
         13 . The method of  claim 1 , wherein the antibody is labeled with a therapeutic agent.