BI 1831169

Finally, the heterologous combination of peptide and viral vaccine elicits the highest proportion of antigen-specific CD8+ T cells in the tumor and tumor-draining lymph nodes. In summary, we provide a basic immune characterization of various factors that affect anti-viral and vaccine target-specific CD8+ T cell proportions and phenotypes, thereby enhancing our vaccinology knowledge for future vaccine regimen designs.

Here, we report the impact of NKG2A blockade on antitumoral CD8 T cell immune response elicited by KISIMA-VSV-GP-TAg vaccination in tumor mouse models. Combination therapy significantly reduced the amount of vaccine-induced exhausted CD8 T cells infiltrating the tumor, resulting in short-term improved tumor growth control and prolonged mouse survival, while it also influenced the establishment of systemic effector memory CD8 T cell response. Taken together, these data show a compartment-dependent effect of NKG2A blockade on cancer vaccine-induced T cell immunity, increasing intratumoral T cell efficacy and attenuating the development of peripheral effector memory CD8 T cell response.

P1, N=190, Recruiting, Boehringer Ingelheim | N=117 --> 190

P1, N=117, Recruiting, Boehringer Ingelheim | Trial primary completion date: Nov 2025 --> May 2027 | Trial completion date: Nov 2026 --> May 2028

Conclusions In conclusion, VSV-GP-CD80Fc is a highly potent and efficacious oncolytic virus. The usage of the CD80-Fc cargo further boosts the therapeutic potential of VSV-GP-based treatments in humans.

Immunization with both vectors protected mice in prophylactic and in therapeutic TC-1 tumor models with HPVp1 being more effective in the prophylactic setting. Taken together, VSV-GP is a promising candidate as therapeutic HPV vaccine and first position of the vaccine antigen in a VSV-derived vector seems to be superior to fifth position.

These studies present a case for a predominantly lytic treatment effect of VSV-GP in a syngeneic mouse lung cancer model.