Combination Therapies Employing GITR Binding Molecules

Abstract

The present invention provides combination therapies that employ a GITR binding molecule in combination with one or more additional agents.

1 - 64 . (canceled) 
     
     
         65 . A method for treating a subject having a tumor, the method comprising administering a GITR-binding antibody, or an antigen-binding fragment thereof, and a therapy, to the subject, wherein the GITR-binding antibody or the antigen-binding fragment acts as a GITR agonist, and the therapy is administered at a separate time from the GITR-binding antibody or the antigen-binding fragment at least once,
 wherein the therapy is a chemotherapeutic agent selected from the group consisting of an antimetabolite, an agent that affects microtubule formation, an alkylating agent, and a cytotoxic antibiotic, and   wherein the GITR-binding antibody or antigen-binding fragment comprises: the heavy chain complementarity determining regions (CDRs) set forth in SEQ ID NOs.: 1, 2, and 4 or in SEQ ID NOs.: 1, 3, and 4; and the light chain CDRs set forth in SEQ ID NOs.: 5, 6, and 7.   
     
     
         66 . The method of  claim 65 , wherein the method results in inhibition of tumor growth. 
     
     
         67 . The method of  claim 65 , wherein the method results in reduction in tumor size. 
     
     
         68 . The method of  claim 65 , wherein the method results in reduction in the number of tumors. 
     
     
         69 . The method of  claim 65 , wherein the method decreases tumor burden in the subject. 
     
     
         70 . The method of  claim 65 , wherein the method prolongs survival of the subject. 
     
     
         71 . The method of  claim 65 , wherein the separate in time administration comprises administration of the therapy to the subject prior to administration of the GITR-binding antibody or the antigen-binding fragment. 
     
     
         72 . The method of  claim 65 , wherein the GITR-binding antibody or the antigen-binding fragment acts synergistically with the therapy. 
     
     
         73 . The method of  claim 72 , wherein the separate in time administration comprises administration of the therapy to the subject prior to administration of the GITR-binding antibody or the antigen-binding fragment. 
     
     
         74 . The method of  claim 65 , wherein the GITR agonist activity of the GITR-binding antibody or the antigen-binding fragment comprises increasing T cell effector responses. 
     
     
         75 . The method of  claim 65 , wherein the chemotherapeutic agent is an antimetabolite. 
     
     
         76 . The method of  claim 75 , wherein the antimetabolite is a nucleoside analogue. 
     
     
         77 . The method of  claim 75 , wherein the antimetabolite is selected from the group consisting of Aminopterin, Methotrexate, Pemetrexed, Raltitrexed, Cladribine, Clofarabine, Fludarabine, Mercaptopurine, Pentostatin, Thioguanine, Capecitabine, Cytaribine, Fluorouracil, Floxuridine, and Gemcitabine. 
     
     
         78 . The method of  claim 65 , wherein the chemotherapeutic agent is an agent that affects microtubule formation. 
     
     
         79 . The method of  claim 78 , wherein the agent that affects microtubule formation is selected from the group consisting of paclitaxel, docetaxel, vincristine, vinblastine, vindesine, vinorelbin, taxotere, etoposide, and teniposide. 
     
     
         80 . The method of  claim 65 , wherein the chemotherapeutic agent is an alkylating agent. 
     
     
         81 . The method of  claim 80 , wherein the alkylating agent is cyclophosphamide. 
     
     
         82 . The method of  claim 65 , wherein the chemotherapeutic agent is a cytotoxic antibiotic. 
     
     
         83 . The method of  claim 82 , wherein the cytotoxic antibiotic is a topoisomerase II inhibitor. 
     
     
         84 . The method of  claim 83 , wherein the topoisomerase II inhibitor is doxorubicin 
     
     
         85 . The method of  claim 65 , wherein the chemotherapeutic agent is Gemcitabine.