Targeting of src-3 in immune cells as an immunomodulatory therapeutic for the treatment of cancer

Abstract

The present disclosure concerns methods and compositions related to cancer treatment comprising targeting of SRC-3 in immune cells, including T cells such as T regulatory cells. The targeting of SRC-3 in T regulatory cells in particular is effective to eradicate tumors in mammals. In specific cases, the T regulatory cells are subjected to CRISPR ex vivo to produce cells suitable for adoptive cell transfer. In some cases, one or more agents that target SRC-3 are also administered to the individual and/or are exposed to the cells prior to administration.

What is claimed is: 
     
         1 . A pharmaceutical composition, comprising engineered immune cells comprising disruption of steroid receptor coactivator-3 (SRC-3). 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the immune cells are T regulatory cells that are CD4+ and CD25+. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the immune cells are CD4+CD25+ FOXP3+ T regulatory cells. 
     
     
         4 . The pharmaceutical composition of  claim 1 , further comprising one or more agents that target SRC-3. 
     
     
         5 . The composition of  claim 4 , wherein the cells and the one or more agents are in the same formulation. 
     
     
         6 . The composition of  claim 4 , wherein the cells and the one or more agents are not in the same formulation. 
     
     
         7 . The composition of  claim 4 , wherein the cells and the one or more agents are configured to be delivered by the same route of administration. 
     
     
         8 . The composition of  claim 4 , wherein the cells and the one or more agents are configured not to be delivered by the same route of administration. 
     
     
         9 . The composition of  claim 4 , wherein the agent that targets SRC-3 is a small molecule inhibitor, an antibody, a protein, a nucleic acid, or a combination thereof. 
     
     
         10 . A pharmaceutical composition, comprising an agent that targets the disruption of SRC-3. 
     
     
         11 . The pharmaceutical composition of  claim 10 , wherein the agent is CRISPR, a transcription activator-like protein (TAL) DNA binding domain, or zinc finger proteins. 
     
     
         12 . The pharmaceutical composition of  claim 10 , wherein the agent targets a T regulatory cell.