Dendritic Cell Immunotherapy with Homologous Antigenic Loading as Adjuvant Treatment for Glioblastoma: Phase I Trial Analysis [RNA-seq]

Glioblastoma is a devastating CNS tumor for which median survival remains only 14-18 months. Homologous antigenic loading provides a powerful PAMP signal that initiates cDC1-like skewing of monocyte-derived DC and downstream development of tissue-homing, cytolytic memory effectors. Here we report results of a phase I trial in which DC vaccines prepared through homologous antigenic loading were administered principally to newly-diagnosed MGMT unmethylated GBM patients. AEs were mild, with none >grade 2 attributable to the regimen. Enrolled patients exhibited post-vaccination elevations in central memory and MPEC cells in peripheral blood, evidence of in situ immune responses by spatial transcriptomics, and a vaccine cell gene signature that correlated with outcomes. One-year OS of the 15/16 MGMT unmethylated newly-diagnosed cohort was 87.5%. Among nine patients who did not receive reoperation, GBM-specific OS was 88.9% with median OS yet-to-be-reached after 17.2 months follow-up among this group and late pseudoprogression notable among long-term survivors. Overall design: Paired DC vaccine, doubly-loaded loaded with both amplified tumor mRNA and lysate, and autologous control samples loaded only with amplified tumor mRNA were normalized to read count, and statistically significant alterations to gene expression between homologous loaded vaccine and autologous, non-homologous control (mRNA-loaded only) were determined across the 18 paired samples.