Gm-csf/cd40l vaccine and checkpoint inhibitor combination therapy

Abstract

A method is disclosed for treating a cancer in a subject. The method comprises administering to the subject a composition comprising a therapeutically effective amount of a checkpoint inhibitor and a therapeutically effective amount of a tumor vaccine. In some embodiments, the tumor vaccine comprises radiated autologous tumor cells and a cell line engineered to express GM-CSF and CD40 ligand. In some embodiments, the checkpoint inhibitor comprises an anti-PD-1 antibody (e.g., BMS 936558), anti-PD-L1 antibody (e.g., cloneM1H1), anti-CTLA-4 antibody (e.g., Ipilimumab, BMS), or any combination thereof.

1 . A method for treating a cancer in a subject, comprising administering to the subject a composition comprising a therapeutically effective amount of an immune checkpoint inhibitor and a therapeutically effective amount of a tumor vaccine. 
     
     
         2 . The method of  claim 1 , wherein the checkpoint inhibitor comprises an anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, or a combination thereof. 
     
     
         3 . The method of  claim 2 , wherein the anti-PD-1 antibody comprises nivolumab. 
     
     
         4 . The method of  claim 1 , wherein the cancer comprises a non-small cell lung cancer. 
     
     
         5 . The method of  claim 1 , wherein the tumor vaccine comprises radiated autologous tumor cells and a cell line engineered to express GM-CSF and CD40 ligand. 
     
     
         6 . The method of  claim 5 , wherein the cell is further engineered to express one more factors selected from the group consisting of IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-15, erythropoietin, GCSF, M-CSF, platelet derived growth factor (PDGF), MSF, FLT-3 ligand, EGF, fibroblast growth factor (FGF), bFGF (FGF-2), FGF-3, FGF-4, FGF-5, FGF-6, FGF-7, insulin-like growth factor1 (IGF-1), insulin-like growth factor 2 (IGF-2); vascular endothelial growth factor (VEGF), IFN-gamma, IFN-alpha, IFN-beta, leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), oncostatin M, stem cell factor (SCF), TGF-α, and TGF-β1. 
     
     
         7 . The method of  claim 5 , wherein the cell is MHC negative. 
     
     
         8 . The method of  claim 5 , wherein the cell is a tumor cell.