Antagonism of the VIP Signaling Pathway

Abstract

Inhibition of the VIP signaling pathway with VIP antagonist is contemplated. In certain embodiments, the disclosure relates to methods of enhancing the immune response to a cell therapy comprising administering a VIP antagonist to a subject in combination with a cell. In certain embodiments, the subject is diagnosed with leukemia or lymphoma, In certain embodiments, the cell is a blood cell, bone marrow cell, leukocyte, T-cell, natural killer cell, a hematopoietic stem cell, a G-CSF mobilized or non-mobilized blood mononuclear cell.

1 - 16 . (canceled) 
     
     
         17 . A method comprising expanding a lymphocyte in vitro by exposing the lymphocyte to a VIP antagonist. 
     
     
         18 . The method of  claim 17 , wherein are lymphocyte is extracted from blood or obtained by leukapheresis. 
     
     
         19 . The method of  claim 17 , wherein the lymphocyte is further exposed to a stimulatory cytokine or an interferon. 
     
     
         20 . The method of  claim 17 , wherein the VIP antagonist is a peptide having a C-terminal amide and is optionally modified with hydrocarbon or polyethylene glycol groups and wherein the peptide has SEQ ID NO: 9, wherein X is M. 
     
     
         21 . The method of  claim 17 , wherein the lymphocyte is further exposed to one or more of interleukin-2 (IL-2), anti-CD3, an allo-reactive feeder, and a tumor antigen. 
     
     
         22 . The method of  claim 17 , wherein the lymphocyte comprises a tumor-infiltrating lymphocyte (TIL). 
     
     
         23 . The method of  claim 17 , wherein the lymphocyte is obtained from a tumor in a subject. 
     
     
         24 . The method of  claim 17 , wherein the lymphocyte comprises a T cell. 
     
     
         25 . The method of  claim 17 , wherein lymphocyte is transduced with a vector encoding a T cell receptor (TCR) that recognizes a cancer antigen. 
     
     
         26 . The method of  claim 17 , further comprising transferring the in vitro expanded lymphocyte into a subject having a cancer. 
     
     
         27 . The method of  claim 26 , further comprising administering a VIP antagonist to the subject. 
     
     
         28 . A method of treating a subject having a cancer, comprising
 obtaining a lymphocyte;   expanding the lymphocyte in vitro;   transferring the in vitro expanded lymphocyte into the subject; and   administering a VIP antagonist to the subject.   
     
     
         29 . The method of  claim 28 , wherein the lymphocyte is extracted from blood or obtained by leukapheresis. 
     
     
         30 . The method of  claim 28 , wherein the lymphocyte is obtained from a tumor in the subject. 
     
     
         31 . The method of  claim 28 , wherein the lymphocyte is expanded in vitro by exposing the lymphocyte to one or more of interleukin-2 (IL-2), anti-CD3, an allo-reactive feeder, and a tumor antigen. 
     
     
         32 . The method of  claim 28 , wherein the lymphocyte is expanded in vitro by exposing the lymphocyte to a VIP antagonist. 
     
     
         33 . The method of  claim 28 , further comprising transducing the lymphocyte with a vector encoding T cell receptors (TCRs) that recognize a cancer antigen prior to transfer. 
     
     
         34 . The method of  claim 28 , wherein the VIP antagonist is a peptide having a C-terminal amide and is optionally modified with hydrocarbon or polyethylene glycol groups and wherein the peptide has SEQ ID NO: 9, wherein X is M.