USE OF EphA4 AND MODULATOR OF EphA4 FOR DIAGNOSIS, TREATMENT AND PREVENTION OF CANCER

Abstract

The present invention relates to methods and compositions designed for the treatment, management, or prevention of cancer, particularly, metastatic cancer. In one embodiment, the methods of the invention comprise the administration of an effective amount of one or more antibodies that bind to EphA4 and agonize EphA4. In another embodiment, the methods of the invention comprise the administration of an effective amount of one or more antibodies that bind to EphA4 and inhibit cancer cell colony formation in soft agar or tubular network formation in three-dimensional basement membrane or extracellular matrix preparation. In another embodiment, the methods of the invention comprise the administration of an effective amount of one or more antibodies that preferentially binds to an EphA4 epitope that is exposed on cancer cells but not non-cancer cells. In another embodiment, the methods of the invention comprise the administration of an effective amount of one or more antibodies that bind to EphA4 with a very low K off to reduce EphA4 expression and, thereby, inhibit tumor cell growth and/or metastasis. The invention also provides pharmaceutical compositions comprising one or more EphA4 antibodies of the invention either alone or in combination with one or more other agents useful for cancer therapy.

1 - 78 . (canceled) 
     
     
         79 . A method of monitoring the efficacy of therapy for cancer in a patient known to or suspected to have cancer, said method comprising:
 a. contacting cells of said patient with an EphA4 antibody that is an EphA4 agonistic antibody, an EphA4 cancer cell phenotype inhibiting antibody, an exposed EphA4 epitope antibody under conditions appropriate for antibody-EphA4 binding; and   b. measuring EphA4 antibody binding to said cells, wherein detecting a higher EphA4 antibody binding level than in a control indicates that the patient has cancer.   
     
     
         80 . The method of  claim 79  wherein said cells are from whole blood, sputum, urine, serum or fine needle aspirates of tumor cell tissue. 
     
     
         81 . The method of  claim 79  wherein said cells are in frozen or fixed tissue or cells from said patient. 
     
     
         82 . The method of  claim 79  wherein said detecting comprises imaging of said EphA4 antibody binding in said patient. 
     
     
         83 . The method of  claim 79  wherein said patient has metastatic cancer. 
     
     
         84 . The method of  claim 79  wherein said EphA4 antibody is an exposed EphA4 epitope antibody. 
     
     
         85 . An EphA4 antibody or antibody fragment that is an EphA4 agonistic antibody, an EphA4 cancer cell phenotype inhibiting antibody, or an exposed EphA4 epitope antibody wherein the variable heavy chain and/or variable light chain amino acid sequence possesses at least 90% amino acid sequence identity with the variable heavy chain or light chain amino acid sequence of EA44, as contained in SEQ IDs NO: 4 and 8, respectively. 
     
     
         86 . The EphA4 antibody of  claim 85  wherein at least three CDRs of said variable light chain and variable heavy chain are identical to the corresponding CDRs in EA44. 
     
     
         87 . The EphA4 antibody of  claim 85  wherein at least four of its CDRs are identical to the corresponding CDRs in EA44. 
     
     
         88 . The EphA4 antibody of  claim 85  wherein at least five of its CDRS are identical to the corresponding CDRs in EA44. 
     
     
         89 . The EphA4 antibody of  claim 85  wherein all six of its CDRs are identical to the corresponding CDRs of EA44. 
     
     
         90 . A cell line which produces an antibody of  claim 85 .