Abstract B053: Allogeneic cancer cell vaccines elicit antitumor immunity independent of MHC compatibility

Abstract Allogeneic cancer cell vaccines have the potential to stimulate antitumor immunity through innate immune activation and indirect antigen presentation by host antigen-presenting cells (APCs). However, the impact of MHC mismatch on CD8+ T cell responses remains unclear. We hypothesized that mismatched MHC haplotypes between the vaccine and host would not impair CD8+ T cell activation, as antigen presentation would occur indirectly via host APCs following phagocytosis of vaccine cells. We further anticipated that allogeneic vaccines would suppress tumor growth through non-specific activation of APCs, triggered by pathogen-associated molecular patterns and danger signals present on the surface of allogeneic cells. To test this, we generated a whole-cell cancer vaccine by silicifying cultured BR5-akt ovarian cancer cells in a solution of 10 mM tetramethyl orthosilicate, 100 mM NaCl, pH 3, for ten minutes at room temperature, followed by incubation at −80 °C and a slow thaw in silicic acid. The surface was then functionalized with polyethyleneimine (PEI), monophosphoryl lipid A (MPL), and CpG oligodeoxynucleotides. FVB mice were challenged intraperitoneally with syngeneic BR5-akt-Luc cells and vaccinated beginning on either day 4 or day 8 post-tumor inoculation. Tumor burden was assessed via bioluminescence imaging, and weight gain was used as a surrogate marker for survival. Across multiple tumor models, vaccinated mice exhibited consistently reduced tumor burden relative to unvaccinated controls. Importantly, therapeutic efficacy was observed using both MHC-matched and mismatched cells, indicating that MHC mismatch did not impair antitumor responses, and importantly, did not cause adverse reactions. These findings support a mechanism in which host APCs mediate indirect antigen presentation and CD8+ T cell priming. Earlier vaccination (day 4) resulted in stronger tumor suppression than delayed vaccination (day 8), underscoring the importance of early immune engagement. In ovarian cancer models, vaccinated mice maintained weight relative to controls, consistent with improved health and survival. Collectively, these findings demonstrate that allogeneic cancer cell vaccines can elicit effective antitumor responses independent of MHC compatibility, supporting their potential as broadly applicable immunotherapies. Citation Format: Ania V. Klas, Lorel Medina, Rita Serda. Allogeneic cancer cell vaccines elicit antitumor immunity independent of MHC compatibility [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Ovarian Cancer Research; 2025 Sep 19-21; Denver, CO. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl):Abstract nr B053.