Neurology Clinical Trial Database
Oncolytic Virus for Recurrent Glioblastoma — Spatial Omics Analysis
Persistent T cell activation and cytotoxicity against glioblastoma following single oncolytic virus treatment
Clinical Question
Does oncolytic herpes virus treatment reprogram the glioblastoma immune microenvironment to enable T cell-mediated tumor killing?
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.
Design
Study Type: Phase 1 dose-escalation with spatial multi-omics analysis
Arms
| Field | Study cohort |
|---|---|
| Intervention | Spatial multi-omics analysis of paired biopsies before/after intratumoral rQNestin34.5v.2 oncolytic herpes simplex virus injection (phase 1 dose-escalation). |
| Duration |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Spatial multi-omics characterization of the immune microenvironment before vs after intratumoral rQNestin34.5v.2 oncolytic herpes virus injection in recurrent glioblastoma. | Primary | ||||
| Not reported | Adverse | No adverse event data extracted for this trial | |||
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
Based on: Oncolytic Virus for Recurrent Glioblastoma — Spatial Omics Analysis (Cell, 2026)
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