Abstracts for the 25th Annual Scientific Meeting of theInternational Society for Biological Therapy of Cancer

Abstract

Two-component tumor mRNA-based vaccines exhibit two principle activities: antigen expression and concomitant immune stimulation. Thus, innate as well as adaptive immune responses are induced. Intradermal vaccination of tumor-bearing mice with the two-component mRNA vaccine mediates a strong anti-tumor response under therapeutic conditions. Depletion experiments demonstrate the requirement of CD8 T cells for the anti-tumor effect and the necessity of CD4 T cell help for the induction of antigen-specific CTLs. FACS analysis of tumor tissue revealed increased infiltration of activated CD8 T cells and their prolonged persistence at the tumor site in response to vaccination. Moreover, therapeutic vaccination inhibited a tumor-induced increase of myeloid derived suppressor cells (MDSCs) in the spleen and at the tumor site. To further elucidate the mechanism of our mRNA-based anti-cancer vaccine, tumor-bearing mice were vaccinated repeatedly and tumors were removed at different time points. Microarray analysis of total mRNA extracted from removed tumors revealed clear differences between vaccinated and control mice. Already after two vaccinations, before the effect on tumor size became visible, a wide variety of immune response related genes was upregulated in vaccinated mice. A large proportion of these genes is associated with activation and cytotoxicity of NK and T cells, Th1 polarization or chemotaxis. Our findings conclusively demonstrate the comprehensive nature of the immune response induced by our mRNA based vaccines and the variety of pathways involved in the anti-tumor effect. Better understanding of the mode of action allows further improvement of our vaccine approach and the selection of potential targets for combination therapies. Additionally, the approach opens new possibilities for targeted monitoring of induced immune responses.