Abstract B080: Improved neoantigen vaccine selection by combining prediction of pMHC presentation and T-cell epitopes

Abstract

The OpenVax group has helped initiate two neoantigen vaccine clinical trials (NCT02721043, NCT02721043) at Mount Sinai based on a simple multiplicative ranking criterion which assigns equal weight to expression and predicted Class I MHC binding affinity of mutated peptides (1). This poster seeks to better ground our ranking method for selecting the contents of neoantigen vaccines in several sources of immunological data. We built a better model of MHC-I presentation on the cell surface by relating RNA expression and MHC affinity to pMHC ligands identified with mass spectrometry (2). Secondly, we trained a model of overall T-cell immunogenicity whose primary input is the predicted pMHC presentation score of any peptide-MHC combination, alongside other features such as similarity to the self proteome. This model is trained on T-cell response data deposited in the Immune Epitope Database (3). Lastly, we assembled a small dataset of peptide sequences used in neoantigen vaccine trials (1,4,5), which are labeled by whether they achieved a CD8+ or CD4+ T-cell response. This dataset allows us to explore several hypotheses about the relationship between immunogenic response and sequence similarity to both the self proteome and pathogenic proteomes. References: 1. Rubinsteyn A, Kodysh J, …, Hammerbacher J. Computational pipeline for the PGV-001 Neoantigen Vaccine Trial. Frontiers in Immunology 2018. 2. Abelin JG, Keskin DB,..., Wu CJ. Mass spectrometry profiling of HLA-associated peptidomes in mono-allelic cells enables more accurate epitope prediction. Immunity 2017. 3. Vita R, Overton JA, …, Peters B. The immune epitope database (IEDB) 3.0. Nucleic Acids Res 2014. [4. Sahin U, Derhovanessian E, …, Tureci O. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature 2017. 5. Ott P, Hu Z, …, Wu CJ. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature 2017. Citation Format: Julia Kodysh, Tim O9Donnell, Ana B. Blazquez, John Finnigan, Nina Bhardwaj, Alex Rubinsteyn. Improved neoantigen vaccine selection by combining prediction of pMHC presentation and T-cell epitopes [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B080.