286 Vaccination by Homologous Antigenic Loading as Adjuvant Therapy for Glioblastoma: Early Analysis of Phase I Results

INTRODUCTION: Glioblastoma (GBM) median survival remains 14-18 months despite aggressive care. Early clinical studies of dendritic cell (DC) vaccination for the adjuvant treatment of GBM suggested clinical benefit, but results were inconclusive. Homologous antigenic loading is an ex vivo technique that leverages p38MAPK and mTORC1 signaling cascades to initiate powerful cDC1-like skewing in monocyte-derived DC, leading to induction of tissue-infiltrating CD161int CD8+ cytolytic memory effectors. METHODS: Patients received perinodal dendritic cell vaccinations concurrently with six weeks of type I interferon in addition to standard of care. Four dose levels from 3.5 x 106 to 3.6 x 107 total vaccine cells were tested. Overall, exclusion criteria were kept minimal. RESULTS: Safety analyses identified no SAEs (> grade 3) likely attributable to the investigational regimen. Tumor immunohistochemistry from early post-vaccination second resections displayed enhanced CD8+ T-cell infiltration. Analysis of post-vaccination circulating PBMC in dose levels 2 through 4 indicated expansions of both CD4+ (13/13) and CD8+ (11/13) central memory T-cell compartments (avg 41% expansion, p=0.0001 and avg 37% expansion, p=0.003, respectively) as well as expansion of CD8+CD127+ T-cells (12/13; avg 61% expansion, p=0.002). Among three patients for whom tissue was obtained pre- and post-vaccination, clinical outcomes could be correlated with transcriptional alterations identified by Visium spatial transcriptomic analysis. With an average 13.4-month follow-up, median survival of this 15/16 MGMT promoter unmethylated cohort has not yet been reached and is statistically greater (p<0.003 by log-rank) than matched historical controls. At the time of abstract submission, 12/16 trial patients remain alive and stable. CONCLUSIONS: The results indicate that this dendritic cell vaccine is safe, potentially efficacious, and can be effectively integrated within existing standards of care.