Augmenting combination immunotherapies with vaccination or costimulatory/inhibitory antibodies for the treatment of cancer Public Deposited

Recently, antibodies that block T cell inhibitory checkpoints have proven to be a beneficial treatment for patients with solid tumors. However, when given as monotherapies a substantial portion of patients remain refractory to treatment. Given the complexities of the interface between tumors and the immune system, alternative therapies are required to treat these patients and elucidating novel therapeutic combinations remains an urgent need. This body of work explores two potential ways to impact tumors that are either devoid of T cell infiltrate or refractory to checkpoint blockade. The first approach addresses cancer vaccination, which can impact patients with “cold” tumors (that lack infiltrating T cells) by priming a new T cell response to tumor-­‐specific antigens. It is poorly understood whether booster vaccinations, commonly used with vaccines against pathogenic microorganisms, inhibit the efficacy of a single vaccination with whole-­‐cell tumor vaccines. We determined that tumor immunogenicity (defined by the protection offered by a single prophylactic vaccination) or addition of the adjuvant GM-­‐CSF (also known as a GVAX vaccine) did not diminish the efficacy of multiple vaccinations, and did not increase inhibitory regulatory T cells. Importantly, the addition of GM-­‐CSF did significantly increase the amount of T cells in the tumors of multiply vaccinated animals. This suggests that the addition of GM-­‐CSF to vaccines correlates with improved trafficking of T cells to the tumor, a benefit that may be useful in cancer vaccination in the future.

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