Abstract 6539: Bioinformatics algorithm of mRNA-4157 identifies neoantigens with pre-existing TIL reactivities in colorectal tumors

Abstract Background: Personalized cancer vaccines (PCVs) encode mutation-derived epitopes (neoantigens) predicted from each tumor's unique set of somatic mutations, and can trigger the activation of neoantigen-specific CD4+ and/or CD8+ T cells to target cancer cells. The accurate prediction of immunogenic neoantigens from a tumor's mutanome, which may contain hundreds of somatic mutations, is crucial for designing an effective PCV. In this study, we evaluated the performance of the bioinformatics algorithm for mRNA-4157, an mRNA-based therapeutic PCV, in identifying neoantigens that are recognized by pre-existing tumor infiltrating lymphocytes (TILs) in a cohort of colorectal cancers shared by the National Cancer Institute (NCI) [1]. Methods: Whole exome and transcriptome sequencing data from 29 patients with microsatellite stable, mismatch repair (MMR)-proficient metastatic colorectal cancer were shared by NCI. All patients had received at least one previous systemic therapy, and neoantigen-reactive TIL populations had been identified from these patients by high-throughput immunologic screening [1]. The same bioinformatics algorithm as used for mRNA-4157 was run on the sequencing data, to generate a vaccine design for each patient that included up to 34 neoantigens. Results: Overall, 41% (26/64) of the neoantigens recognized by CD8+ or CD4+ TILs according to the NCI assay were included in the vaccines designed by the mRNA-4157 bioinformatics algorithm. For 61% (18/29) of the patients, at least one neoantigen with demonstrated CD8+ or CD4+ TIL reactivity was included in the vaccines designed. For 28% (8/29) of the patients, all neoantigens associated with demonstrated CD8+ or CD4+ TIL reactivities were included in the vaccines designed. Conclusion: The bioinformatics algorithm for mRNA-4157 is able to predict and select neoantigens with pre-existing TIL reactivities based on human ex vivo assays for vaccine designs with high accuracy. [1] Parkhurst MR, et al. Unique Neoantigens Arise from Somatic Mutations in Patients with Gastrointestinal Cancers. Cancer Discov. 2019 Aug;9(8):1022-1035. Citation Format: Shan Zhong, Ben Breton, Wei Zheng, Iain McFadyen, Kristen Hopson, Joshua Frederick, Robert S. Meehan, Tal Zaks. Bioinformatics algorithm of mRNA-4157 identifies neoantigens with pre-existing TIL reactivities in colorectal tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6539.