Grunwitz et al. studied immunity provoked by E7 RNA-LPX, a liposome-encapsulated mRNA encoding human papillomavirus 16 E7 oncoprotein fused to the MHC class I signal sequence and transmembrane and cytoplasmic domains. Given intravenously to mice, E7 RNA-LPX expanded antigen-specific effector and memory T cell populations. In submucosal (orthotopic) and subcutaneous syngeneic mouse E7+ tumor models, E7 RNA-LPX induced intratumoral and systemic proinflammatory innate and adaptive immune responses, regression of and protection from rechallenge with E7+ tumors, and conversion of one model to anti-PD-L1 sensitivity.
Contributed by Paula Hochman
HPV16 infections are associated with a variety of cancers and there is compelling evidence that the transforming activity of HPV16 critically depends on the expression of the viral oncoproteins E6 and E7. Therapeutic cancer vaccines capable of generating durable and specific immunity against these HPV16 antigens hold great promise to achieve long-term disease control. Here we show in mice that HPV16 E7 RNA-LPX, an intravenously administered cancer vaccine based on immuno-pharmacologically optimized antigen-encoding mRNA, efficiently primes and expands antigen-specific effector and memory CD8(+) T cells. HPV-positive TC-1 and C3 tumors of immunized mice are heavily infiltrated with activated immune cells and HPV16-specific T cells and are polarized towards a proinflammatory, cytotoxic and less immune-suppressive contexture. E7 RNA-LPX immunization mediates complete and durable remission of progressing tumors. Circulating memory T cells are highly cytotoxic and protect from tumor rechallenge. Moreover, E7 RNA-LPX immunization sensitizes anti-PD-L1 refractory tumors to checkpoint blockade. In conclusion, our data highlight the potential of HPV16 RNA-LPX for the treatment of HPV-driven cancers.
Author Info: (1) Biopharmaceutical New Technologies (BioNTech) Corporation, Mainz, Germany. Research Center for Immunotherapy (FZI), University Medical Center Mainz, Mainz, Germany. (2) TRON -
Author Info: (1) Biopharmaceutical New Technologies (BioNTech) Corporation, Mainz, Germany. Research Center for Immunotherapy (FZI), University Medical Center Mainz, Mainz, Germany. (2) TRON - Translational Oncology at the University Medical Center of the Johannes Gutenberg University gGmbH, Mainz, Germany. (3) TRON - Translational Oncology at the University Medical Center of the Johannes Gutenberg University gGmbH, Mainz, Germany. (4) TRON - Translational Oncology at the University Medical Center of the Johannes Gutenberg University gGmbH, Mainz, Germany. (5) TRON - Translational Oncology at the University Medical Center of the Johannes Gutenberg University gGmbH, Mainz, Germany. (6) Biopharmaceutical New Technologies (BioNTech) Corporation, Mainz, Germany. TRON - Translational Oncology at the University Medical Center of the Johannes Gutenberg University gGmbH, Mainz, Germany. (7) Biopharmaceutical New Technologies (BioNTech) Corporation, Mainz, Germany. TRON - Translational Oncology at the University Medical Center of the Johannes Gutenberg University gGmbH, Mainz, Germany. (8) Biopharmaceutical New Technologies (BioNTech) Corporation, Mainz, Germany. (9) Biopharmaceutical New Technologies (BioNTech) Corporation, Mainz, Germany. TRON - Translational Oncology at the University Medical Center of the Johannes Gutenberg University gGmbH, Mainz, Germany.
