Tumor specific antibody

Abstract

The present invention provides the amino acid and nucleic acid sequences of heavy chain and light chain complementarity determining regions of a tumor specific antibody. In addition, the invention provides tumor-specific antibodies and immunoconjugates comprising the tumor-specific antibody attached to a toxin or label, and methods and uses thereof. The invention also relates to diagnostic methods and kits using the tumor-specific antibodies of the invention.

1 - 107 . (canceled) 
     
     
         108 . A binding protein that binds to the 5-v8 interface of CD44E. 
     
     
         109 . The binding protein of  claim 108  wherein the binding protein is an antibody. 
     
     
         110 . The binding protein of  claim 109  wherein the antibody is an antibody fragment. 
     
     
         111 . The binding protein of  claim 110  wherein the antibody fragment is a Fab, Fab′, F(ab′) 2 , scFv, dsFv, ds-scFv, dimers, minibodies, diabodies, and multimers thereof or bispecific antibody fragments. 
     
     
         112 . A composition comprising any one of the binding proteins of  claim 108  with a pharmaceutically acceptable excipient, carrier, buffer or stabilizer. 
     
     
         113 . An immunotoxin comprising (1) a binding protein according to  claim 108  that binds to the 5-v8 interface of CD44E on or in a cancer cell, attached to (2) a cancer therapeutic that is cytotoxic, cytostatic or otherwise prevents or reduces the ability of the cancer cells to divide and/or metastasize. 
     
     
         114 . The immunotoxin of  claim 113  wherein the cancer therapeutic is a toxin, such as a ribosome-inactivating polypeptide, and optionally wherein the toxin is selected from the group consisting of gelonin, Bouganin, saproin, ricin, ricin A chain, bryodin, diphtheria, restrictocin, and  Pseudomonas  exotoxin A, and preferably wherein the toxin is modified Bouganin or a truncated form of  Pseudomonas  exotoxin A that consists of amino acids 252-608. 
     
     
         115 . The immunotoxin of  claim 113  wherein the immunotoxin is internalized by the cancer cell. 
     
     
         116 . A composition comprising the immunotoxin of  claim 113  with a pharmaceutically acceptable excipient, carrier, buffer or stabilizer. 
     
     
         117 . A method for treating cancer in a subject in need thereof comprising administering to said subject a pharmaceutically effective amount of the binding protein of  claim 108 . 
     
     
         118 . The method of  claim 117  wherein the 5-v8 interface of CD44E comprises the amino acid sequence ATNMDSSHSIT. 
     
     
         119 . The method of  claim 117  wherein the binding protein is an antibody. 
     
     
         120 . The method of  claim 119  wherein the antibody is an antibody fragment. 
     
     
         121 . The method of  claim 120  wherein the antibody fragment is a Fab, Fab′, F(ab′) 2 , ScFc, dsFv, ds-scFV, dimers, minibodies, diabodies and multimers thereof or bispecific antibody fragments. 
     
     
         122 . The method of  claim 117  wherein the binding protein is conjugated to a cancer therapeutic that is cytotoxic, cytostatic, or otherwise prevents or reduces the ability of cancer cells to divide and/or metastasize. 
     
     
         123 . The method of  claim 122  wherein the cancer therapeutic is a toxin. 
     
     
         124 . The method of  claim 123  wherein the toxin is a ribosome inactivating protein. 
     
     
         125 . The method of  claim 124  wherein the toxin is selected from the group consisting of gelonin, Bouganin, saporin, ricin, ricin A chain, bryodin, diphtheria, restictocin, and  pseudomonas  exotoxin A. 
     
     
         126 . The method of  claim 125  wherein the toxin is modified Bouganin. 
     
     
         127 . The method of  claim 125  wherein the toxin is a truncated form of  pseudomonas  exotoxin A that consists of amino acids 252-608. 
     
     
         128 . The method of  claim 117  wherein the cancer is breast cancer. 
     
     
         129 . The method of  claim 128  wherein the binding protein is administered before, during or after surgical intervention. 
     
     
         130 . The method of  claim 117  further comprising administering one or more additional anticancer drugs to said subject. 
     
     
         131 . The method of  claim 130  wherein the one or more additional anticancer drugs is administered prior to, during or after administration of the binding protein.