Abstract IA019: Addressing genomic heterogeneity in glioblastoma personalized vaccine design

Abstract Glioblastoma is a highly lethal brain cancer that is known for extensive intratumoral genomic heterogeneity. This characteristic makes it difficult to comprehensively identify a set of tumor-unique neoantigens suitable for developing a personalized vaccine for each patient. Our collaborative work has helped to refine this therapeutic approach, encompassing three FDA-IND clinical trials, with increasing refinement. In practice, we utilize multi-region sampling of the resected GBM from each patient to gain an appreciation of region-specific and -shared small variants (SNVs and indels) and their respective neoantigenic properties using pVACseq. A combination of region-specific and -shared neoantigens is advanced for vaccine design, which is administered post-resection in newly diagnosed GBM patients. In cases where, due to progression, post-vaccine tissues are available for study, we perform extensive immunogenomic profiling to evaluate changes in the tumor immune microenvironment and in T cell clonality. We will present results from our most recent trial, including data from nine patients enrolled onto the trial and immunogenomic comparisons of a short-term and long-term responder. Citation Format: Elaine R Mardis, Elizabeth A.R. Garfinkle, Tanner Johanns, Katherine E. Miller, Gavin P Dunn. Addressing genomic heterogeneity in glioblastoma personalized vaccine design [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr IA019.