Methods of Treating Glioblastoma

Abstract

In certain embodiments, this disclosure relates to conjugates comprising GM-CSF and IL-7 and uses related thereto, e.g., enhancing the adaptive immune system. Typically, the GM-CSF and IL-7 are connected by a polymer linker, e.g., polypeptide. In certain embodiments, the disclosure relates to nucleic acids encoding these polypeptide conjugates, vectors comprising nucleic acid encoding polypeptide conjugates, and protein expression systems comprising these vectors such as infectious viral particles and host cells comprising such nucleic acids.

What is claimed: 
     
         1 . A method of treating glioblastoma comprising administering an effective amount of autologous T cells comprising a vector encoding a conjugate comprising a GM-CSF polypeptide and an IL-7 polypeptide having the amino acid sequence of SEQ ID NO: 1 to a subject in need thereof. 
     
     
         2 . The method of  claim 1 , wherein the T cells are derived from peripheral blood mononuclear cells or splenocytes. 
     
     
         3 . The method of  claim 1 , wherein the autologous T cells are further activated by mixing the T cells with αCD3/CD28 antibodies and the conjugate under conditions such that CD8+ T cells expand. 
     
     
         4 . A method of treating glioblastoma comprising administering into a tumor of a subject in need thereof an effective amount of a vector encoding a conjugate comprising a GM-CSF polypeptide and an IL-7 polypeptide having the amino acid sequence of SEQ ID NO: 1. 
     
     
         5 . The method of  claim 4  further comprising administering an anti-CTLA-4 antibody to the subject in need thereof. 
     
     
         6 . The method of  claim 5  wherein the anti-CTLA-4 antibody is ipilimumab or tremelimumab. 
     
     
         7 . The method of  claim 4  further comprising administering bevacizumab to the subject in need thereof.