Oncolytic Virus for Recurrent Glioblastoma — Spatial Omics Analysis
(2026)Objective
To characterize the immune response to intratumoral oncolytic herpes virus in recurrent GBM using spatial multi-omics
Study Summary
• Intratumoral rQNestin34.5v.2 induced persistent T cell activation in GBM.
• Spatial omics revealed granzyme B+ CD8 T cell proximity to apoptotic tumor cells correlated with survival.
• Spatial omics revealed granzyme B+ CD8 T cell proximity to apoptotic tumor cells correlated with survival.
Intervention
Intratumoral rQNestin34.5v.2 (oncolytic herpes simplex virus) injection
Inclusion Criteria
Recurrent glioblastoma, candidates for stereotactic injection followed by surgical resection
Study Design
Arms: Single-arm: intratumoral rQNestin34.5v.2 with pre/post tissue analysis
Patients per Arm: Phase 1 dose-escalation cohort
Outcome
GzmB+ CD8 T cell proximity to apoptotic tumor cells correlated with survival (P<0.05). Persistent T cell activation signatures post-treatment. Myeloid reprogramming from immunosuppressive to inflammatory. Tumor-selective viral replication confirmed.
Bottom Line
Intratumoral rQNestin34.5v.2 induced persistent T cell activation in GBM. Spatial omics revealed granzyme B+ CD8 T cell proximity to apoptotic tumor cells correlated with survival.
Major Points
- Phase 1 trial of intratumoral oncolytic herpes virus (rQNestin34.5v.2) in recurrent GBM with paired spatial multi-omics analysis.
- Granzyme B+ CD8 T cells in proximity to apoptotic tumor cells correlated with prolonged survival (P<0.05) — first spatial evidence of active immune killing in GBM.
- Post-treatment tumors showed persistent T cell activation signatures vs immunosuppressive pre-treatment profiles.
- Immunosuppressive myeloid populations reprogrammed toward M1/inflammatory phenotype after virus treatment.
- Viral replication confirmed in tumor tissue but not normal brain — demonstrating tumor selectivity.
- Published in Cell — landmark spatial omics study in neuro-oncology immunology.
Study Design
- Study Type
- Phase 1 dose-escalation with spatial multi-omics analysis
Limitations & Criticisms
- Phase 1 — very small sample size, no control arm for efficacy assessment
- Spatial omics findings are correlative — causal relationship between T cell proximity and tumor killing not proven
- Requires surgical resection for tissue analysis — limits applicability to operable tumors
- Long-term survival outcomes and clinical efficacy not the focus of this study
- Single virus agent — combination with checkpoint inhibitors not yet tested in this setting