Phase Ib Trial Shows Safety of Personalized Dendritic Cell Vaccine for Newly Diagnosed Glioblastoma

A phase Ib clinical trial published on July 4, 2026, demonstrates the safety and preliminary efficacy of ZSNeo-DC, a personalized neoantigen-pulsed autologous dendritic cell vaccine for newly diagnosed glioblastoma. In the eleven-patient study, the vaccine was well tolerated with only minor grade 1 or 2 adverse events. Patients showed significant immune activation and a median progression-free survival of 16.2 months, offering a promising precision medicine approach to treating aggressive brain tumors.

Phase Ib trial results

• ▪The phase Ib clinical trial of the personalized dendritic cell vaccine ZSNeo-DC was registered under the trial number NCT04968366
• ▪A single-arm, open-label phase Ib trial evaluated the safety of a personalized neoantigen-pulsed autologous dendritic cell vaccine, ZSNeo-DC, in eleven newly-diagnosed glioblastoma patients

Personalized neoantigen identification

• ▪Researchers sequenced the tumor exome of enrolled glioblastoma patients to identify individualized tumor-specific neoantigens resulting from mutations
• ▪The personalized vaccine was engineered by isolating dendritic cells from patients and pulsing them with tumor-specific neoantigens

Safety profile findings

• ▪The ZSNeo-DC vaccine was well tolerated by patients, with adverse events predominantly classified as grade 1 or 2
• ▪Only two grade-1 or grade-2 febrile adverse events were recorded as treatment-related during the phase Ib trial of ZSNeo-DC

Enhanced immune response activation

• ▪Immune monitoring revealed enhanced activation of CD8+ cytotoxic T-cells specific to the neoantigenic peptides and increased infiltration into residual tumor tissue
• ▪Patients receiving ZSNeo-DC showed a median 7.2-fold increase in peripheral neoantigen-specific immune response after the third vaccination
• ▪Following ZSNeo-DC vaccination, the activated-to-exhausted ratio of memory T cells and the clonal evenness of the T cell receptor repertoire increased significantly

Progression-free survival extension

• ▪Newly-diagnosed glioblastoma patients treated with ZSNeo-DC demonstrated a median progression-free survival of 16.2 months
• ▪The median overall survival of the eleven newly-diagnosed glioblastoma patients treated with ZSNeo-DC was not reached during the trial

Manufacturing scalability challenges

• ▪Manufacturing autologous vaccines requires sophisticated genomic and immunologic analyses and cell processing capabilities completed within a clinically relevant timeframe
• ▪Investigators utilized next-generation sequencing, bioinformatics pipelines, and optimized cell culture protocols to streamline neoantigen identification and generate vaccine batches swiftly