Methods and compositions for the treatment of melanoma

Abstract

Provided herein are methods and compositions for the treatment of melanoma using anti-tumor immune cells treated with a PTD-MYC fusion protein (e.g., an HIV TAT-MYC fusion protein).

1 .- 20 . (canceled) 
     
     
         21 . A method for preparing modified immune cells for melanoma therapy, comprising contacting one or more immune cells in vitro with a MYC fusion polypeptide, wherein the immune cells are from a donor that has been exposed to one or more tumor antigens and wherein the MYC fusion peptide comprises (i) a protein transduction domain; (ii) a MYC polypeptide sequence and are reactive to a tumor-specific antigen. 
     
     
         22 . The method of  claim 21 , wherein the one or more modified immune cells are derived from primary immune cells isolated from a subject having melanoma. 
     
     
         23 . The method of  claim 21 , further comprising expanding the primary immune cells in vitro prior to contacting with the MYC fusion peptide. 
     
     
         24 . The method of  claim 21 , further comprising expanding the primary immune cells following contacting with the MYC fusion peptide. 
     
     
         25 . The method of  claim 21 , wherein the cells are expanded using an anti-CD3 antibody or irradiated allogenic feeder cells. 
     
     
         26 . The method of  claim 21 , wherein the cells are expanded in the presence of an exogenous cytokine. 
     
     
         27 . The method of  claim 26 , wherein the cytokine is interleukin-2. 
     
     
         28 . The method of  claim 21 , wherein the MYC fusion peptide translocates to the nucleus of the immune cell. 
     
     
         29 . The method of  claim 21 , wherein the MYC fusion peptide exhibits a biological activity of MYC. 
     
     
         30 . The method of  claim 21 , wherein the MYC fusion peptide further comprises one or more molecules that link the protein transduction domain and the MYC polypeptide. 
     
     
         31 . The method of  claim 21 , wherein the MYC fusion peptide comprises a MYC fusion peptide with the following general structure:
 protein transduction domain-X-MYC sequence,   wherein —X— is molecule that links the protein transduction domain and the MYC sequence.   
     
     
         32 . The method of  claim 21 , wherein the protein transduction domain sequence is a TAT protein transduction domain sequence. 
     
     
         33 . The method of  claim 32 , wherein the TAT protein transduction domain sequence is selected from the group consisting of TAT[48-57] and TAT[57-48]. 
     
     
         34 . The method of  claim 21 , wherein the MYC fusion peptide comprises SEQ ID NO: 1. 
     
     
         35 . The method of  claim 21 , wherein the MYC fusion peptide is acetylated. 
     
     
         36 . The method of  claim 21 , wherein the one or more modified immune cells have antitumor activity. 
     
     
         37 . The method of  claim 21 , wherein the one or more modified immune cells have antitumor activity against melanoma cells in the subject. 
     
     
         38 . The method of  claim 21 , wherein the one or more modified immune cells comprise one or more anergic immune cells. 
     
     
         39 . The method of  claim 21 , wherein the one or more immune cells comprises one or more lymphocytes. 
     
     
         40 . The method of  claim 39 , wherein the one or more lymphocytes comprise a T cell, a B cell, an NK, or any combination thereof.