Methods of treating neoplastic astrocytoma

Abstract

The present invention relates to specific binding members, particularly antibodies and fragments thereof, which bind to amplified epidermal growth factor receptor (EGFR) and to the de2-7 EGFR truncation of the EGFR. In particular, the epitope recognized by the specific binding members, particularly antibodies and fragments thereof, is enhanced or evident upon aberrant post-translational modification. These specific binding members are useful in the diagnosis and treatment of cancer. The binding members of the present invention may also be used in therapy in combination with chemotherapeutics or anti-cancer agents and/or with other antibodies or fragments thereof.

What is claimed: 
     
         1 . A method of treating a neoplastic astrocytoma in a human subject, the method comprising administering to the subject a therapeutically effective amount of an isolated anti-Epidermal Growth Factor Receptor (EGFR) antibody comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 164, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 166. 
     
     
         2 . The method according to  claim 1 , wherein the heavy chain comprises the constant region set forth in SEQ ID NO: 43. 
     
     
         3 . The method according to  claim 1 , wherein the light chain comprises the constant region set forth in SEQ ID NO: 48. 
     
     
         4 . The method according to  claim 3 , wherein the antibody is an IgG isotype. 
     
     
         5 . The method according to  claim 4 , wherein the IgG isotype is an IgG1 isotype. 
     
     
         6 . The method according to  claim 1 , wherein the antibody is conjugated to a cytotoxic agent. 
     
     
         7 . The method according to  claim 1 , wherein the antibody is administered in combination with temozolomide. 
     
     
         8 . A method of treating a neoplastic astrocytoma in a human subject, the method comprising administering to the subject a therapeutically effective amount of an isolated anti-Epidermal Growth Factor Receptor (EGFR) antibody, wherein the antibody is capable of binding EGFR on tumors containing amplifications of the EGFR gene, wherein cells of said tumors contain multiple copies of the EGFR gene, and on tumors that express the truncated version of the EGFR receptor de2-7, wherein the antibody does not bind to the de2-7 EGFR junctional peptide consisting of the amino acid sequence of SEQ ID NO:13, wherein the antibody binds to an epitope within the sequence of residues 287-302 (SEQ ID NO:14) of human wild-type EGFR, and wherein said antibody does not comprise a heavy chain variable region sequence having the amino acid sequence set forth in SEQ ID NO:2 and does not comprise a light chain variable region sequence having the amino acid sequence set forth in SEQ ID NO:4. 
     
     
         9 . The method according to  claim 8 , wherein the antibody is an IgG isotype. 
     
     
         10 . The method according to  claim 9 , wherein the IgG isotype is an IgG1 isotype. 
     
     
         11 . The method according to  claim 8 , wherein the antibody is conjugated to a cytotoxic agent. 
     
     
         12 . The method according to  claim 8 , wherein the antibody is administered in combination with temozolomide.