Unbiased testing of several hundred tumor-specific single nucleotide variants of a tumor for protective immunogenicity and CD8+ response reveals surprises.

• DOI: 10.4049/jimmunol.200.supp.57.15
• Publication Date: 2023-01-01T11:26:22Z
• Authors: Cory A Brennick; Mariam M George; Adam T Hagymasi; Tatiana V Shcheglova; Sahar Al Seesi; Ion I Mandoiu; Pramod K Srivastava
• Keywords: 0301 basic medicine; 03 medical and health sciences; 3. Good health

Abstract Somatic mutations in cancer cells can give rise to new MHC epitopes referred as neoepitopes. Neoepitopes have been clearly demonstrated elicit an antigen specific T cell response, which are capable of mediating targeted killing cells. Despite recent advancements, exactly what criteria make a good neoepitope for personalized therapy is currently unknown. Here, using syngeneic tumor C57BL/6 mice, named FABF, we present results exhaustive and exhausting study where tested hundreds long peptides each containing single nucleotide variant (SNV) (with the mutation center peptide) their ability rejection independently, CD8+ response. We observe that (i) about 2% all SNVs lead generation mediate any significant degree; (ii) peptide alone elicits modest protection, combination stronger protective immunity, (iii) neoepitopes poor binding affinity I, positive values Differential Agretopic Index (1). (iv) Even though responses CD8-mediated, there no correlation between neoepitope’s CD8 response rejection. Some these observations inconsistent with some aspects current consensus defining characteristics