BI 1831169

Taken together, the 11 newly identified epitopes facilitate the monitoring of anti-viral CD8+ T cells, which will aid the preclinical development of novel VSV-GP variants. This epitope-specific monitoring also serves as proof of concept for the potential future application of anti-viral immunomonitoring in clinical trial settings.

To mitigate neurotoxicity and improve therapeutic efficacy, genetically-engineered strains, such as VSV-∆M51, VSV-mIFNβ, and VSV-GP, have been developed...Ongoing research continues to explore strategies for improving systemic delivery, minimizing off-target effects, and enhancing viral persistence within the tumor bed. Further investigation and clinical translation will determine the full potential of VSV-based viroimmunotherapy in cancer treatment.

P1, N=46, Not yet recruiting, Boehringer Ingelheim

Taken together, we have demonstrated that oncolytic virotherapy using VSV-GP encoding IL-12 induces CD8+ T cell responses characterized by an LLEC phenotype, a cell population that is likely a crucial component of antitumor immunity.

P1, N=190, Recruiting, Boehringer Ingelheim | Trial primary completion date: May 2027 --> Dec 2027

P1, N=190, Recruiting, Boehringer Ingelheim | Trial completion date: May 2028 --> Oct 2028

We identified distinct patterns of viral biodistribution and replication across tumor and nontumor sites but no major differences in biodistribution, off-tumor cell tropism, or immune cell responses between tumor-free and tumor-bearing mouse models. Our findings characterize key cellular changes following systemic exposure to VSV-GP, provide a better understanding of a nonclinical permissive tumor model for OV assessment, and demonstrate how current molecular pathology methods can provide a bridge between traditional biodistribution and pathology readouts.

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.