CTIM-30. THE PRIVATE AND RECURRING ANTIGENIC PROFILE OF HUMAN MEDULLOBLASTOMA

Abstract

Abstract BACKGROUND Identifying tumor rejection antigens remains a major barrier to developing effective immunotherapeutics and their application to pediatric brain tumors. We performed a multi-faceted computer algorithm, the Open Reading Frame Antigen Network (O.R.A.N.), on medulloblastoma transcription profiles and predicted antigens across a broad array of antigen classes. METHODS Patient-specific HLA haplotypes were called via customized Optitype and Phlat algorithms. Only expressed mutations such as single nucleotide variations, small indels, gene fusions, and Tumor Associated Antigens (TAAs) were used for antigenic epitope predictions. TAAs were selected only if expressed > 1 transcript per million (TPM) in tumor and the standardized expression across a human tissue database. Immunogenic TAA epitopes were screened against a customized human proteomic library to guarantee that epitopes were not shared by other expressed isoforms or genes. Immune deconvolution with single cell RNASeq integration was leveraged for teasing out medulloblastoma immunologic landscape. RESULTS We hypothesized that medulloblastomas are immunologically heterogeneous and express genes with limited normal tissue expression that may serve as targets for immunotherapy. In this study, most neoantigens from medulloblastoma patients were found private suggesting a personalized neoantigen based therapy was on demand. In addition, recurring neoantigens were common in SHH but composed only a small proportion of putative antigens in WNT, Group 3 and Group 4 patients. However, recurring TAAs were found to be more commonly expressed in the latter three molecular subgroups but not in SHH. Together, combining personalized neoantigen vaccine and taking advantage of recurring TAAs approach may maximize anti medulloblastoma effect. CONCULSION Medulloblastoma is a heterogeneous disease, and the current standard of care treatments don’t take that into account. Newer, and safer, patient-specific treatment approaches are required to treat high-risk patients who are not cured by the standard therapies .Cellular immunotherapy might be key to improving survival and avoiding morbidity.