Oncolytic Virus rQNestin34.5v.2 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
Randomization:
Blinding: None (single-arm)
Follow-up Duration: Variable
Centers: 0
Countries:
Sample Size: 0
Analysis: Spatial transcriptomics, paired pre/post tissue analysis
Inclusion Criteria
- Recurrent glioblastoma
- Candidate for stereotactic injection and subsequent surgical resection
- Failed standard therapy (surgery, radiation, temozolomide)
Exclusion Criteria
- Active infection
- Immunosuppressive therapy
- Not suitable for surgery
Arms
| Field | rQNestin34.5v.2 |
|---|---|
| Intervention | Intratumoral oncolytic herpes simplex virus injection followed by surgical resection |
| Duration | Single treatment with tissue analysis |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Persistent T cell activation in post-treatment tumors | Secondary | Significant activation signatures | |||
| Myeloid reprogramming | Secondary | Shift from M2 to M1/inflammatory phenotype | |||
| Viral replication selectivity | Secondary | Confirmed in tumor, absent in normal brain | |||
| Dose-limiting toxicity | Adverse | Manageable safety profile |
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 rQNestin34.5v.2 for Recurrent Glioblastoma — Spatial Omics Analysis (Cell, 2026)
Citation: Cell. 2026.
Content summarized and formatted by NeuroTrials.ai.