Agonist fusion protein for cd40 and ox40 and uses thereof

Abstract

Provided is a fusion protein comprising an agonist for CD40 and an agonist for OX40. Compositions comprising the fusion protein and methods of use are also provided.

What is claimed is: 
     
         1 . A fusion protein comprising Component A and Component B, wherein Component A comprises an ectodomain of OX40L comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 3 and Component B comprises a polypeptide agonist for CD40, and further comprising a linker between Components A and B. 
     
     
         2 . The fusion protein of  claim 1 , wherein the polypeptide agonist for CD40 comprises at least a portion of the ectodomain of CD40 ligand (CD40L). 
     
     
         3 . The fusion protein of  claim 2 , wherein the CD40L comprises the amino acid sequence of any one of SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10. 
     
     
         4 . The fusion protein of  claim 2 , wherein the ectodomain is from human CD40L. 
     
     
         5 . The fusion protein of  claim 1 , wherein the polypeptide agonist for CD40 is a derivative of an agonist monoclonal anti-CD40 antibody, the derivative selected from scFvCD40, V H C H CD40, and V H HCD40. 
     
     
         6 . The fusion protein of  claim 1 , wherein the linker comprises any one of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, or SEQ ID NO: 16. 
     
     
         7 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the fusion protein of  claim 1 . 
     
     
         8 . A method of stimulating the immune system of a patient in need thereof, the method comprising administering a therapeutically effective amount of the fusion protein of  claim 1  to the patient. 
     
     
         9 . The method of  claim 8 , wherein the administering step further comprises administering a vaccine to the patient. 
     
     
         10 . The method of  claim 9 , wherein the fusion protein and the vaccine are administered simultaneously. 
     
     
         11 . The method of  claim 9 , wherein the fusion protein and the vaccine are administered sequentially. 
     
     
         12 . A method of stimulating the immune system of a patient in need thereof, comprising administering a therapeutically effective amount of the pharmaceutical composition of  claim 7  to the patient. 
     
     
         13 . The method of  claim 8 , wherein the patient has a proliferative disorder. 
     
     
         14 . The method of  claim 13 , wherein the proliferative disorder is cancer. 
     
     
         15 . The method of  claim 14 , wherein the cancer is a hematological B cell malignancy or melanoma. 
     
     
         16 . The method of  claim 12 , wherein the patient has a proliferative disorder. 
     
     
         17 . The method of  claim 16 , wherein the proliferative disorder is cancer. 
     
     
         18 . The method of  claim 17 , wherein the cancer is a hematological B cell malignancy or melanoma.