Hung Trinh, Senior VP of Operations at Seneca Therapeutics and CMC/MFG Consultant and Managing Director at Vertex Biopharm Consulting, shared a post on LinkedIn:
“Persistent T cell activation and cytotoxicity against glioblastoma following single oncolytic virus treatment in a clinical trial. We evaluated rQNestin34.5v.2 (CAN-3110, linoserpaturev), an oHSV-1 in which expression of the viral ICP34.5 gene was controlled by the nestin promoter, a gene overexpressed in GBM.
These results suggest combination therapies with oHSV, including PD-1-VEGF bispecific antibodies that have shown clinical activity in other cancer types
- Oncolytic virus treatment induces deep and persistent T cell infiltration in human GBM
- Proximity of granzyme B+ CD8 T cells to apoptotic tumor cells correlates with patient survival
- Pre-existing tumor-infiltrating T cells expand upon oncolytic virus treatment
- Spatial TCR mapping shows continued engagement of GBM cells by expanded T cells
This study was registered at ClinicalTrials.gov (NCT03152318). Here, we provide in situ evidence of ongoing T cell-mediated cytotoxicity against tumor cells at late time points following single treatment, with deep and persistent T cell infiltration into tumor regions. Shorter distances between cleaved caspase-3+ tumor cells and granzyme B+ T cells were associated with longer progression-free survival following treatment.
Pre-existing tumor-infiltrating T cells expanded locally upon treatment, correlating with longer overall patient survival. T cells with an early activation program closely interacted with tumor cells and were strongly enriched upon treatment. Viral remnants were restricted to necrotic regions, while T cells infiltrated deeply into live tumor regions. These data demonstrate that single oncolytic virus treatment can expand pre-existing T cell clones and trigger persistent T cell-mediated immunity against GBM.”
Title: Persistent T cell activation and cytotoxicity against glioblastoma following single oncolytic virus treatment in a clinical trial
Authors: Maxime Meylan, Ye Tian, Lijian Wu, Alexander Ling, Daniel Kovarsky, Graham Barlow, Linh Nguyen, Jason Pyrdol, Sascha Marx, Lucas Westphal, Julius Michel, Nicolas Gonzalez Castro, Sydney Dumont, Andres Santos, Itay Tirosh, Mario Suvà, Antonio Chiocca, Kai Wucherpfennig
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