Vaccination with in vitro transcribed RNA encoding tumor antigens is an emerging approach in cancer immunotherapy. Attempting to further improve RNA vaccine efficacy, we have explored combining RNA with immunomodulators such as rapamycin. Rapamycin, the inhibitor of mTOR (mammalian target of rapamycin) has been originally used for immunosuppression. Recent reports in mouse systems, however, suggest that mTOR inhibition may enhance the formation and differentiation of the memory CD8+ T cell pool. As memory T cell formation critically impacts the outcome of vaccination aproaches, we studied the impact of rapamycin on the in vivo primed RNA vaccine-induced immune response using the chicken ovalbumin expressing B16 melanoma model in C57BL/6 mice. Our data shows that treatment with rapamycin in the effector-to-memory transition phase skews the vaccine induced immune response towards formation of a quantitatively and qualitatively superior memory pool and results in a better recall response. Immune cell infiltrations of tumors from these mice display a favourable ratio of effector versus suppressor cell populations. Survival of mice treated with the combination of RNA vaccination with rapamycin is significantly longer (91,5 days) than mice in the control groups receiving only one of these compounds (32 and 46 days, respectively). Our findings indicate that rapamycin enhances therapeutic efficacy of antigen-specific CD8+ T cells induced by RNA vaccination and propose its further clinical exploration as component of a immuntherapeutic regimen.
- Received April 24, 2013.
- Revision received August 22, 2013.
- Accepted September 8, 2013.
- Copyright © 2013, American Association for Cancer Research.