Therapy with clostridium perfringens enterotoxin to treat ovarian and uterine cancer

Abstract

The invention discloses high levels of receptors for Clostridium perfringens enterotoxin (CPE) have been found in ovarian cancer and uterine cancer tissue samples. In addition, successful in vivo treatment of a mouse model of ovarian cancer with intraperitoneal injection of CPE is disclosed. High levels of Ep-CAM protein is also disclosed in ovarian cancer tissue samples. Thus, the invention provides a method of treating ovarian cancer and uterine cancer by administering CPE. The invention also provides a method of treating cancer in a mammal involving intraperitoneal administration of CPE, where at least some cancerous cells are located in or adjacent to the peritoneal cavity of the mammal. The invention also provides a method of treating ovarian cancer involving administering an anti-Ep-CAM antibody. The invention also provides a method of treating cancers expressing claudin-3 or claudin-4 by administering an antibody against claudin-3 and/or an antibody against claudin-4. The invention also provides a method of protecting a mammal from CPE toxicity involving administering a protective agent that binds to claudin-3 and/or claudin-4 and inhibits CPE binding to claudin-3 and/or claudin-4.

1 - 24 . (canceled) 
     
     
         25 . A method of treating cancer in a mammal comprising:
 administering to the mammal a therapeutically effective amount of a cytotoxic agent that binds specifically to claudin-3 and/or claudin-4;   wherein the cancer is ovarian cancer or uterine cancer.   
     
     
         26 . The method of  claim 25  wherein the cytotoxic agent is an antibody that binds specifically to claudin-3 and/or claudin-4. 
     
     
         27 . The method of  claim 25  wherein the antibody comprises residues 290-319 of SEQ ID NO:1 or a fragment thereof that binds specifically to claudin-3 and/or claudin-4. 
     
     
         28 . The method of  claim 25  wherein the cytotoxic agent comprises (i) residues 290-319 of SEQ ID NO:1 or a fragment thereof that binds specifically to claudin-3 and/or claudin-4; coupled to (ii) a cytotoxic moiety. 
     
     
         29 . An anticancer agent comprising:
 a moiety that binds specifically to claudin-3 and/or claudin-4; coupled to a cytotoxic moiety;   wherein the agent is effective to kill tumor cells overexpressing claudin-3 and/or claudin-4 in vitro or in vivo, and wherein the agent is not  Clostridium perfringens  enterotoxin.   
     
     
         30 . The anticancer agent of  claim 29  wherein the agent is effective to treat cancer in a mammal in vivo, wherein the cancer comprises tumor cells overexpressing claudin-3 and/or claudin-4. 
     
     
         31 . The anticancer agent of  claim 29  wherein the cytotoxic moiety is an anticancer chemotherapeutic agent. 
     
     
         32 . The anticancer agent of  claim 29  wherein the cytotoxic moiety is a moiety that stimulates cell killing by immune system components. 
     
     
         33 . The anticancer agent of  claim 32  wherein the cytotoxic moiety is an antibody Fc. 
     
     
         34 . The anticancer agent of  claim 32  wherein the cytotoxic moiety is interleukin-2. 
     
     
         35 . The anticancer agent of  claim 29  wherein the cytotoxic moiety is a therapeutic radionuclide. 
     
     
         36 . The anticancer agent of  claim 29  wherein the moiety that binds specifically to claudin-3 and/or claudin-4 comprises residues 290-319 of SEQ ID NO:1 or a fragment thereof that binds specifically to claudin-3 and/or claudin-4.