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RNA-sequencing of primary human glioblastoma resected tissue before and after a personalized, neoantigen-based vaccine plus poly-ICLC (NeoVax); tissues from a Phase 1 clinical trial

ABSTRACT: Glioblastoma (GBM) patient outcomes remain low despite surgery, radiation, and chemotherapy. There are few immunotherapy options due to the lack of tumor immunogenicity. Several clinical trials have reported promising results with cancer vaccines, although most trials have used single tumor region sequencing to identify targetable antigens. This approach limits the antigen pool due to the heterogeneity of GBM tumors. We have implemented multisector sequencing to identify targetable neoantigens across the GBM tumor landscape that were then incorporated into personalized peptide vaccines called NeoVax. Here, we report the findings of four subjects enrolled on the trial. Following NeoVax, we observed a clonal expansion of CD8+ T cells in the peripheral blood that, when expanded in vitro, were reactive to, on average, half of the NeoVax neoantigens tested by IFN-g ELISPOT, including BRAF V600E in one subject. A post-NeoVax tumor biopsy was resected from one subject and also showed evidence of infiltrating CD8+ T cell clonal expansion. Although the patients enrolled in this trial did not achieve remission, this pilot study demonstrates the feasibility of NeoVax and the importance of multisector sampling for neoantigen screening.

ORGANISM(S): Homo sapiens

PROVIDER: GSE237936 | GEO | 2024/04/12

REPOSITORIES: GEO

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