Combination immune therapy and cytokine control therapy for cancer treatment

Abstract

Compositions disclosed herein, and methods of use thereof included those for inhibiting or reducing the incidence of cytokine release syndrome or cytokine storm in a subject undergoing CAR T-cell therapy, wherein the subjects are administered compositions including apoptotic cells or apoptotic cell supernatants. In certain instances compositions and methods of use thereof disclosed herein do not reduce the efficacy of the CAR T-cell cancer therapy. Disclosed herein are also compositions and methods of use thereof for decreasing or inhibiting cytokine production in a subject experiencing cytokine release syndrome or cytokine storm including administration of a composition including apoptotic cells or an apoptotic cell supernatant.

1 . A composition comprising (a) chimeric antigen receptor-expressing T-cells (CAR T-cells) and a pharmaceutically acceptable excipient, and (b) either early apoptotic cells or an early apoptotic cell supernatant and a pharmaceutically acceptable excipient, wherein said early apoptotic cells are ≥40% Annexin V +  and ≤15% propidium iodide + , and wherein said early apoptotic cells are peripheral blood mononuclear cells. 
     
     
         2 . The composition of  claim 1 , wherein said apoptotic cells are pooled third party donor cells. 
     
     
         3 . The composition of  claim 1 , wherein said early apoptotic cells are autologous to a subject administered said composition. 
     
     
         4 . The composition of  claim 1 , wherein said apoptotic cell supernatant comprises an apoptotic white blood cell supernatant. 
     
     
         5 . The composition of  claim 4 , wherein said white blood cells are selected from the group consisting of phagocytes, macrophages, dendritic cells, monocytes, B cells, T cells, and NK cells. 
     
     
         6 . The composition of  claim 1 , wherein said CAR T-cells and said either apoptotic cells or apoptotic cell supernatant are comprised in separate compositions. 
     
     
         7 . The composition of  claim 1 , further comprising an additional agent selected from the group comprising a CTLA-4 blocking agent, an alpha-1 anti-trypsin or fragment thereof or analogue thereof, a tellurium-based compound, or an immune modulating agent, or any combination thereof. 
     
     
         8 . The composition of  claim 7 , wherein said additional agent or any combination thereof is comprised with the CAR T-cells, or with either the apoptotic cells or the apoptotic cell supernatant, or is comprised in a separate composition.