Abstract
Abstract BACKGROUND Pediatric brain tumors present a heterogeneous group of neoplasms with limited treatment options, especially at relapse. Hence, innovative therapeutic strategies are imperative. Immunotherapy, specifically immunogenomics, utilizing personalized vaccines based on tumor-specific neoantigens, has emerged as a promising option in other tumors. However, the feasibility of this approach in pediatric brain tumors remain largely unexplored. METHODS This single institution feasibility study focuses on sequencing analyses of pediatric brain tumors to identify mutant tumor-specific antigens. The study employs tumor/normal exome sequencing and cDNA-capture sequencing to identify and confirm mutant antigens, respectively. An epitope prediction algorithm prioritizes these antigens with subsequent confirmation of binding to HLA class I molecules. The neoantigen DNA vaccine strategy, utilizing a polyepitope DNA vaccine, is designed to target up to 20 prioritized antigens. The TDS-IM v2.0 device facilitates the administration of the vaccine. The primary objective of the study is to determine the feasibility of adjuvant personalized neoantigen DNA vaccine administration in patients with recurrent or refractory pediatric brain tumors. RESULTS We anticipate the identification of actionable neoantigens in pediatric brain tumors to support the potential efficacy of personalized DNA vaccines. The proposed sequencing strategies, epitope prediction algorithm, and in vitrobinding studies aim to establish a comprehensive methodology for neoantigen identification and prioritization. During the meeting, we will present the study background, rationale, detailed methodology, and design to inform the brain tumor community of this study. CONCLUSION This feasibility study is poised to provide essential insights into the development of personalized neoantigen DNA vaccines for recurrent or refractory pediatric brain tumors and aims to demonstrate safety, feasibility, and potential efficacy in targeting mutant tumor-specific antigens. The findings from this study will lay the groundwork for future clinical trials, evaluating the impact of personalized immunotherapy on progression-free and overall survival rates in this challenging patient population.
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