Selection of targeted neoantigens for ongoing personalized cancer vaccine trials at Dana Farber Cancer Institute 2189

Abstract Description Leveraging the specificity of personalized tumor antigens, neoantigen targeting personalized cancer vaccines (PCVs) have great potential as an effective cancer therapy. Accurate prediction and selection of the most immunogenic neoepitopes for inclusion the vaccines is critical for their success. We have previously demonstrated robust PVC immunogenicity in phase I trials of melanoma and glioblastoma multiforme (GBM). We completed a trial in renal cell carcinoma (RCC) NCT02950766, in which the PCVs were immunogenic in all patients, targeted cancer driver mutations, and importantly demonstrated in vitro reactivity to autologous patient tumors. Neoantigen selection pipeline currently supports clinical trials by employing state-of-art immunopeptidome-trained epitope prediction algorithms. For the PCV platform (NeoVax), we design up to 24 synthetic long peptides, eighteen to thirty-two amino acids in length. Algorithms incorporate prediction for HLA Class I neoantigens, as well as for synthesizability and solubility. Highly expressed neoantigens and neoantigens originating from cancer drivers are prioritized. For future iterations, we aim to enhance pipeline by including novel classes of neoantigens, such as those derived from endogenous human retroviruses, fusion epitopes, novel or unannotated open reading frames (nuORFs), and neoantigens identified through immunopeptidome analysis. The neoantigen selection pipeline is currently supporting seven cancer vaccine trials at DFCI. Funding Sources Department of Defense CDMRP (KC190130). Department of Defense (KCRP AKCI-ECI, W81XWH-20-1-0882), DF/HCC Kidney Cancer SPORE P50 CA101942. NHLBI 1R01HL157174-01A1. NCI-1R01CA229261, Francis and Adele Kittredge Family Immuno-Oncology and Melanoma Research Fund, Fisher Family Fund, Morgan Family Fund for Melanoma Research, Susana and Bruce Hampton Research Fund, Faircloth Family Research Fund Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)