Immunoconjugates targeting cd46 and methods of use thereof

Abstract

Disclosed herein are immunoconjugates comprising a CD46 binding domain and effector agent. Further provided herein are methods of treating cancer comprising administering to a subject having cancer a pharmaceutical composition comprising immunoconjugates comprising a CD46 binding domain and effector agent.

What is claimed is: 
     
         1 . A method of treating a human subject having a cancer comprising cells that overexpress CD46, the method comprising administering to the human subject a pharmaceutical composition comprising an immunoconjugate comprising,
 (i) an antibody that specifically binds CD46, conjugated to   (ii) monomethylauristatin E or monomethylauristatin E via a linker,   
       wherein the pharmaceutical composition is administered at a dose determined from the body weight of the human subject, 
       wherein the dose is from about 1.2 mg immunoconjugate per kg body weight of the human subject to about 3.0 mg immunoconjugate per kg body weight of the human subject. 
     
     
         2 . The method of  claim 1 , wherein the linker comprises maleimidocaproyl-valine-citrulline-para-amino benzyloxycarbonyl. 
     
     
         3 . The method of  claim 1 , wherein the pharmaceutical composition is administered at a dose of about 1.2 mg immunoconjugate per kg body weight of the human subject. 
     
     
         4 . The method of  claim 1 , wherein the pharmaceutical composition is administered at a dose of about 1.8 mg immunoconjugate per kg body weight of the human subject. 
     
     
         5 . The method of  claim 1 , wherein the pharmaceutical composition is administered at a dose of about 2.1 mg immunoconjugate per kg body weight of the human subject. 
     
     
         6 . The method of  claim 1 , wherein the pharmaceutical composition is administered at a dose of about 2.4 mg immunoconjugate per kg body weight of the human subject. 
     
     
         7 . The method of  claim 1 , wherein the pharmaceutical composition is administered at a dose of about 2.7 mg immunoconjugate per kg body weight of the human subject. 
     
     
         8 . The method of  claim 1 , wherein the pharmaceutical composition is administered at a dose of about 3.0 mg immunoconjugate per kg body weight of the human subject. 
     
     
         9 . The method of  claim 1 , wherein the body weight of the human subject is an actual body weight. 
     
     
         10 . The method of  claim 1 , wherein the body weight of the human subject is an adjusted body weight. 
     
     
         11 . The method of  claim 1 , wherein the body weight of the human subject is:
 an actual body weight of the human subject if the actual body weight of the human subject is less than an adjusted body weight of the subject;   an adjusted body weight of the human subject if
 the actual body weight of the human subject is greater than or equal to an adjusted body weight of the subject, and 
 the adjusted body weight of the human subject is less than 100 kg; or 
   100 kg if the adjusted body weight of the human subject is greater than or equal to 100 kg.   
     
     
         12 . The method of  claim 11 , wherein the pharmaceutical composition is administered to the human subject every 7 days, every 14 days, every 18 days, every 21 days, or every 30 days. 
     
     
         13 . The method of  claim 11 , wherein the immunoconjugate is administered to the human subject every 21 days over at least three cycles. 
     
     
         14 . The method of  claim 1 , wherein the pharmaceutical composition is administered via intravenous infusion. 
     
     
         15 . The method of  claim 1 , wherein the cancer is metastatic castration resistant prostate cancer. 
     
     
         16 . The method of  claim 14 , wherein the cancer has higher CD46 expression than a non-cancerous tissue of the same tissue type from the subject or from a healthy individual. 
     
     
         17 . The method of  claim 16 , further comprising detecting the CD46. 
     
     
         18 . The method of  claim 17 , wherein the detecting comprises immunofluorescence microscopy or immunohistochemistry. 
     
     
         19 . The method of  claim 17 , wherein the detecting comprises flow cytometry.