Hofer et al. showed that vaccinating mice bearing uninflamed tumors with a heterologous regimen of an adjuvanted protein-based prime and a VSV variant boost expressing the same antigen increased antitumor activity relative to a homologous regimen. The TME and dLNs had increased numbers/functionality of antigen-specific CD8+ T cells and cross-presenting cDC1s, and CD4+ Th1 cell skewing. In an inflamed tumor model, a heterologous multi-epitope vaccine regimen prolonged host survival, decreased Tregs in tumors, and increased cross-presenting DCs in dLN and CD8+ T cells expressing multiple antigen specificities in tumors and peripherally.
Contributed by Paula Hochman
ABSTRACT: Heterologous prime-boost settings with a protein vaccine and the viral vector vesicular stomatitis virus, both expressing tumor-associated antigens (KISIMA-TAA and VSV-GP-TAA), have been previously shown to generate potent antitumor immunity. In the cold TC-1 model (HPV antigen) and the immune-infiltrate MC-38 model (Adpgk, Reps1 and Rpl18 neo-antigens), we further investigated pivotal immune cells that educate CD8+ T cells. Heterologous prime-boost vaccination induced a superior antitumor response characterized by the increase in number and functionality of antigen-specific CD8+ T cells, recruitment of cross-presenting dendritic cells, and polarization of CD4+ T cells towards an antitumor Th1 phenotype within the tumor and tumor-draining lymph nodes, turning the cold TC-1 tumor into a hot, inflamed tumor. In the inflamed MC-38 tumor model, treatment combination markedly prolonged the overall survival of mice. Treatment with multi-epitope vaccines also induced high frequencies of multiple antigen specificities in the periphery and in the tumor. Prime-boost treatment reduced tumor-infiltrating regulatory CD4+ T cells whilst increasing cross-presenting dendritic cells in tumor-draining lymph nodes. In conclusion, heterologous prime-boost vaccination possesses the ability to induce a potent anti-tumor response in both immune-excluded and immune-infiltrated mouse tumor models. Additionally, this study highlights the design of a multi-epitope vaccine for cancer immunotherapy.
Author Info: (1) Christian Doppler Laboratory for Viral Immunotherapy of Cancer, Medical University of Innsbruck, Peter-Mayr-Stra§e 4b, 6020 Innsbruck, Austria. Division of Virology, Medical Un
Author Info: (1) Christian Doppler Laboratory for Viral Immunotherapy of Cancer, Medical University of Innsbruck, Peter-Mayr-Stra§e 4b, 6020 Innsbruck, Austria. Division of Virology, Medical University of Innsbruck, Peter-Mayr-Stra§e 4b, 6020 Innsbruck, Austria. AMAL Therapeutics, Fondation Pour Recherches Mdicales, Avenue de la Roseraie 64, 1205 Geneva, Switzerland. Boehringer Ingelheim International GmbH, 55216 Ingelheim, Germany. (2) AMAL Therapeutics, Fondation Pour Recherches Mdicales, Avenue de la Roseraie 64, 1205 Geneva, Switzerland. Boehringer Ingelheim International GmbH, 55216 Ingelheim, Germany. (3) AMAL Therapeutics, Fondation Pour Recherches Mdicales, Avenue de la Roseraie 64, 1205 Geneva, Switzerland. Boehringer Ingelheim International GmbH, 55216 Ingelheim, Germany. (4) AMAL Therapeutics, Fondation Pour Recherches Mdicales, Avenue de la Roseraie 64, 1205 Geneva, Switzerland. Boehringer Ingelheim International GmbH, 55216 Ingelheim, Germany. (5) Division of Virology, Medical University of Innsbruck, Peter-Mayr-Stra§e 4b, 6020 Innsbruck, Austria. (6) Christian Doppler Laboratory for Viral Immunotherapy of Cancer, Medical University of Innsbruck, Peter-Mayr-Stra§e 4b, 6020 Innsbruck, Austria. Division of Virology, Medical University of Innsbruck, Peter-Mayr-Stra§e 4b, 6020 Innsbruck, Austria. (7) AMAL Therapeutics, Fondation Pour Recherches Mdicales, Avenue de la Roseraie 64, 1205 Geneva, Switzerland. Boehringer Ingelheim International GmbH, 55216 Ingelheim, Germany. (8) AMAL Therapeutics, Fondation Pour Recherches Mdicales, Avenue de la Roseraie 64, 1205 Geneva, Switzerland. Boehringer Ingelheim International GmbH, 55216 Ingelheim, Germany.
