Uses of anti-cd40 antibodies

Abstract

Methods for treating a human patient for a cancer or pre-malignant condition that is associated with CD40-expressing cells are provided, where the human patient is heterozygous or homozygous for FcγRIIIa-158F (genotype V/F or F/F). Also provided are methods of inhibiting antibody production by B cells in a human patient who is heterozygous or homozygous for FcγRIIIa-158F (genotype V/F or F/F). The methods comprise administering to the human patient a therapeutically or prophylactically effective amount of an anti-CD40 antibody. Methods and kits for identifying a human patient with a cancer or pre-malignant condition that is treatable with an anti-CD40 antibody and which is refractory to treatment with rituximab (Rituxan®), as well as methods and kits for selecting an antibody therapy for treatment of a human patient having a cancer or pre-malignant condition that is refractory to treatment with rituximab (Rituxan®), are also provided. The methods of the present invention find use in treatment of cancers and pre-malignant conditions that are associated with CD40-expressing cells. These methods are particularly advantageous with respect to cancers and pre-malignant conditions that are associated with cells expressing both CD40 and CD20, as the methods enable the treatment of patients having a cancer or pre-malignant condition that is refractory to therapy with other oncotherapeutic agents such as anti-CD20 antibodies.

That which is claimed: 
     
         1 . A method for identifying a human patient with a cancer or pre-malignant condition treatable with an anti-CD40 antibody and which is refractory to treatment with rituximab (Rituxan®), comprising:
 a) identifying a human patient with a cancer or pre-malignant condition that is associated with CD40-expressing cells; and 
 b) determining said human patient's FcγRIIIa-158 genotype (V/V, V/F or F/F); 
 
       wherein said cancer or pre-malignant condition is treatable with an anti-CD40 antibody if said human patient is heterozygous or homozygous for FcγRIIIa-158F (genotype V/F or F/F). 
     
     
         2 . A method according to  claim 1 , wherein said human patient is refractory to therapy with an anti-cancer agent. 
     
     
         3 . A method according to  claim 2 , wherein said human patient is refractory to therapy with an anti-CD20 monoclonal antibody. 
     
     
         4 . A method according to  claim 3 , wherein said anti-CD20 monoclonal antibody is rituximab (Rituxan®). 
     
     
         5 . A method according to  claim 3 , wherein said human patient is resistant to therapy with an anti-CD20 monoclonal antibody. 
     
     
         6 . A method according to  claim 5 , wherein said anti-CD20 monoclonal antibody is rituximab (Rituxan®). 
     
     
         7 . A method according to  claim 3 , wherein said human patient is non-responsive to therapy with an anti-CD20 monoclonal antibody. 
     
     
         8 . A method according to  claim 7 , wherein said anti-CD20 monoclonal antibody is rituximab (Rituxan®). 
     
     
         9 . A method for selecting an antibody therapy for treatment of a human patient having a cancer or pre-malignant condition which is refractory to treatment with rituximab (Rituxan®), comprising:
 a) identifying a human patient having a cancer or pre-malignant condition that is associated with CD40-expressing cells and which is refractory to treatment with rituximab (Rituxan®); and 
 b) determining said human patient's FcγRIIIa-158 genotype (V/V, V/F or F/F); 
 
       wherein if said human patient is heterozygous or homozygous for FcγRIIIa-158F (genotype V/F or F/F), an anti-CD40 antibody is selected for treatment of said cancer or pre-malignant condition. 
     
     
         10 . A method according to  claim 9 , wherein said human patient is refractory to therapy with an anti-cancer agent. 
     
     
         11 . A method according to  claim 10 , wherein said human patient is refractory to therapy with an anti-CD20 monoclonal antibody. 
     
     
         12 . A method according to  claim 11 , wherein said anti-CD20 monoclonal antibody is rituximab (Rituxan®). 
     
     
         13 . A method according to  claim 11 , wherein said human patient is resistant to therapy with an anti-CD20 monoclonal antibody. 
     
     
         14 . A method according to  claim 13 , wherein said anti-CD20 monoclonal antibody is rituximab (Rituxan®). 
     
     
         15 . A method according to  claim 11 , wherein said human patient is non-responsive to therapy with an anti-CD20 monoclonal antibody. 
     
     
         16 . A method according to  claim 15 , wherein said anti-CD20 monoclonal antibody is rituximab (Rituxan®).