Dendritic Cell Immunotherapy with Homologous Antigenic Loading as Adjuvant Treatment for Glioblastoma: Phase I Trial Analysis [Spatial Transcriptome]

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: Samples used for Visium spatial transcriptomic analysis were FFPE blocks of brain tumor tissue adhered to analysis slides in 5 micron slices. In the analysis, tissue derived from pre-vaccination first operation was compared to post-vaccination second operation.