ATIM-32. PERSONALIZED NEOANTIGEN-TARGETING VACCINE GENERATES ROBUST SYSTEMIC AND INTRATUMORAL T CELL RESPONSES IN GLIOBLASTOMA (GBM) PATIENTS

Abstract

BACKGROUND: The impact of individualized neoepitope vaccination targeting neoantigens arising from tumor-specific mutations for GBM, a low mutation burden tumor with an immunologically cold tumor microenvironment, as well as that of concurrently administered dexamethasone (dex), are unknown. METHODS: Individualized vaccination of up to 20 synthetic, long neoepitope peptides with high predicted HLA binding affinity admixed with poly-ICLC, were administered subcutaneously using a prime-boost schedule after RT to newly diagnosed, MGMT unmethylated, at least partially resected, GBM patients without progression after radiation (RT) in our phase 1b study. RESULTS: 9 of 10 screened patients had sufficient (10) identified neoepitope peptides. 8 patients without progression after RT received vaccine consisting of a median of 12 peptides (range, 7-20) beginning a median of 19.9 wks (range 17.1-24.7) after surgery. Adverse events were limited to infrequent grade 1/2 local reactions and fatigue. Median PFS and OS were 7.5 mths (90% CI: 6.2, 9.7) and 16.8 mths (90% CI: 9.6, 21.3). Evaluation of neoepitope-specific immune responses and tumor immune infiltrate analyses were performed on five patients with pre- and post-vaccination samples. Three patients on dex for post-RT edema during vaccine had no immune responses and no change in tumor infiltrating effector cells. In contrast 2 patients not on dex had robust, de novo immune responses against multiple predicted personal neoantigens including polyfunctional neoantigen-specific CD4+ and CD8+ T cell responses that were enriched for memory and activated phenotypes as well as increased numbers of tumor-infiltrating CD4+ and CD8+ T cells. T cell receptor analysis from one patient identified identical clonotypes isolated from post-vaccination tumor tissue and peripheral blood including two clonotypes specific for ARHGAP35, a neoantigen targeted by vaccination. CONCLUSIONS: Individualized, multi-neoepitope vaccines are feasible, safe and capable of generating systemic and intra-tumoral immune responses in GBM patients that appear to be abrogated by dex.