Constitutive expression of costimulatory ligands on adoptively transferred t lymphocytes

Abstract

The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing at least one of an antigen-recognizing receptor and a co-stimulatory ligand and methods of use therefore for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

What is claimed is: 
     
         1 . An immunoresponsive cell comprising an exogenous co-stimulatory ligand and a receptor that binds an antigen, wherein the exogenous co-stimulatory ligand is CD80. 
     
     
         2 . The immunoresponsive cell of  claim 1 , wherein the immunoresponsive cell is a T cell or a Natural Killer (NK) cell. 
     
     
         3 . The immunoresponsive cell of  claim 2 , wherein the immunoresponsive cell is a T cell. 
     
     
         4 . The immunoresponsive cell of  claim 3 , wherein the T cell is a cytotoxic T lymphocyte (CTL), and a regulatory T cell. 
     
     
         5 . The immunoresponsive cell of  claim 1 , wherein the co-stimulatory ligand is constitutively or inducibly expressed. 
     
     
         6 . The immunoresponsive cell of  claim 1 , wherein the antigen is a tumor antigen or a pathogen antigen. 
     
     
         7 . The immunoresponsive cell of  claim 1 , wherein the antigen is selected from the group consisting of prostate-specific membrane antigen (PSMA), Carcinoembryonic Antigen (CEA), IL13Rα, Her-2, CD19, NY-ESO-1, HIV-1 Gag, Lewis Y, Mart-1, gp100, tyrosinase, WT-1, hTERT, and mesothelin. 
     
     
         8 . The immunoresponsive cell of  claim 1 , wherein the receptor is a chimeric antigen receptor (CAR) or a T cell receptor (TCR). 
     
     
         9 . The immunoresponsive cell of  claim 8 , wherein the receptor is a CAR. 
     
     
         10 . The immunoresponsive cell of  claim 9 , wherein the CAR comprises a (chain signaling domain. 
     
     
         11 . The immunoresponsive cell of  claim 10 , wherein the CAR further comprises a domain that provides a costimulatory signal. 
     
     
         12 . The immunoresponsive cell of  claim 11 , wherein the costimulatory signal is a CD28 costimulatory signal. 
     
     
         13 . An immunoresponsive cell comprising a receptor that binds to an antigen, and a nucleic acid molecule encoding an exogenous CD80. 
     
     
         14 . The immunoresponsive cell of  claim 13 , wherein the nucleic acid molecule is comprised on a vector. 
     
     
         15 . The immunoresponsive cell of  claim 14 , wherein the vector is a viral vector. 
     
     
         16 . The immunoresponsive cell of  claim 15 , wherein the viral vector is a retroviral vector. 
     
     
         17 . An immunoresponsive cell comprising: a) a receptor that binds to an antigen, and b) a nucleic acid encoding a recombinant co-stimulatory ligand which is a heterologously expressed cytokine that is selected from the group consisting of an IL-2, an IL-12 and an IL-21. 
     
     
         18 . A method of treating or preventing a neoplasm in a subject, comprising administering to the subject the immunoresponsive cell of  claim 1 . 
     
     
         19 . A method of treating or preventing a neoplasm in a subject, comprising administering to the subject the immunoresponsive cell of  claim 17 . 
     
     
         20 . An immunoresponsive cell comprising an exogenous co-stimulatory ligand and a receptor that binds an antigen, wherein the exogenous co-stimulatory ligand is 4-1BBL, a combination of 4-1BBL and CD80, or a combination of 4-1BBL and CD86.