Abstract 856: Exploiting the molecular mimicry for preventive/therapeutic cancer vaccine development

Abstract Shared tumor antigens are needed for developing off-the-shelf preventive/therapeutic cancer vaccines. To this aim, shared mutated neoantigens (TSAs) cannot be exploited for highly prevalent tumors in the majority of worldwide cancer patients. Therefore, TAAs must be used, which may suffer from the potential immunological tolerance. Analogue peptides with improved antigenicity and immunogenicity, able to elicit a cross-reactive T cell response are needed. To this aim, non-self-antigens derived from microorganisms (MoAs) may be of great benefit. We will describe several examples of MoAs sharing sequence homology with TAAs (“molecular mimicry”), able to elicit a cross-reacting CD8+ T cell response. In particular, the homology to cancer testis TAA (e.g. MAGE-A1) allows to develop cancer vaccines useful for several tumor types, “one-vaccine-for-many-tumors”. In conclusion, non-self MoAs should be selected and included in preventive/therapeutic cancer vaccines with a more potent anti-tumor efficacy compared to those based on TAAs. This would allow the development of ready to be used “off-the-shelf” cancer vaccines for the global population of patients affected by one or more cancer types (Tagliamonte M, et al., Molecular mimicry and cancer vaccine development. Mol Cancer. 2023 Apr 26;22(1):75. doi: 10.1186/s12943-023-01776-0). Citation Format: Maria Tagliamonte, Beatrice Cavalluzzo, Angela Mauriello, Concetta Ragone, Biancamaria Cembrola, Simona Mangano, Luigi Buonaguro. Exploiting the molecular mimicry for preventive/therapeutic cancer vaccine development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 856.