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 granulocyte- macrophage colony-stimulating factor (GM-CSF) and cluster of differentiation 40 (CD40) ligand. In some embodiments, the checkpoint inhibitor comprises an anti-programmed death-1 (anti-PD-1) antibody (e.g., BMS 936558), anti-programmed death ligand-1 (anti-PD-L1) antibody (e.g., cloneMIHI), anti-cytotoxic T lymphocyte antigen-4 (anti-CTLA-4) antibody (e.g., Ipilimumab, BMS), or any combination thereof.

Description

[0001] This application claims the benefit of US Provisional Application No. 62 / 171,829, filed June 5, 2015, the entire contents of which are incorporated herein by reference. Background technique [0002] It has been shown that cancer has multiple mechanisms to prevent the activation of the immune response and to evade it. Therefore, a single treatment, such as immunization with a vaccine, may not be sufficient for clinical efficacy. [0003] Summary of the invention [0004] Methods for treating cancer in a subject (subject) are disclosed. The method includes 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, a tumor vaccine comprises irradiated (irradiated) autologous tumor cells and an engineered cell line expressing GM-CSF and a CD40 ligand. [0005] In some instances, the vaccine comprises a mixture of one, two or more human l...

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Therefore, a single treatment, such as immunization with a vaccine, may not be sufficient for clinical efficacy

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