Tumor membrane vesicle-based vaccine immunotherapy inhibits tumor growth and metastasis of squamous cell carcinoma of head and neck in mice

Abstract

Abstract Head and neck cancer is a leading cause of cancer related deaths accounting for approximately 3% of all cancer related mortalities in the US. Currently, there is no cure for the advanced squamous cell carcinoma of the head and neck (SCCHN) thus development of efficacious therapies is urgently needed. To test whether vaccine-induced immunity inhibits tumor growth, we investigated efficacy of a tumor membrane-based vaccine (TMV) immunotherapy in murine SCCHN models. The MOC1, MOC2 and SCC VII tumors grown subcutaneously in syngeneic mice were harvested to generate TMVs. TMVs were then protein transferred with glycolipid-anchored immunostimulatory molecules GPI-B7.1 and GPI-IL-12 to generate the TMV vaccine. Mice were vaccinated with TMV vaccine after tumor cell challenge (therapeutic) and tumor growth was monitored every 3 days. Survival was then assessed using a Kaplan-Meier survival curve and significance determined using a Log-rank test for comparison analysis. The TMV vaccine inhibited tumor growth and improved the survival of mice challenged with MOC1 or SCC VII tumor cells. Interestingly, combination of anti-PD1 antibody with TMV vaccine decreased MOC1 tumor growth. However, MOC2 (poorly immunogenic tumor) did not respond to anti-PD1 or anti-CTLA-4 antibody therapy but significantly inhibited by TMV vaccine. MOC2 cells metastasize to the lungs in control mice but it is significantly inhibited in mice administered with TMV vaccine. TMV vaccine increased the infiltration of CD4+ and CD8+ T cells into the tumors suggesting that TMV vaccine converts cold tumors into hot tumors. These observations suggest that TMV vaccines can be harnessed to develop an effective immunotherapy for squamous cell carcinoma of the head and neck.