Phase I Trial Reports Median PFS of 16.1 Months With Repeated Doses of Engineered Gamma-Delta T Cells in Newly Diagnosed Glioblastoma

The study enrolled 13 adults with newly diagnosed glioblastoma after resection and chemoradiation. Patients received one to six doses of autologous DeltEx DRI cells engineered to resist temozolomide via lentiviral MGMT expression. Doses were given every 28 days during maintenance chemotherapy. No dose-limiting toxicities, cytokine release syndrome, or neurotoxicity occurred. Median PFS reached 9.9 months across all patients and 16.1 months in the repeated-dose cohort; median overall survival was 19.5 months in that group.

Standard therapy (Stupp regimen) yields median PFS of approximately 6.9 months and OS of 14.6 months. The observed doubling of PFS with repeated dosing suggests that sustained intracranial delivery of chemotherapy-resistant gamma-delta T cells can extend local immune control during the maintenance phase when tumor burden is lowest. This approach differs from systemic CAR-T or checkpoint strategies that have shown limited CNS penetration and higher toxicity in glioblastoma.

The trial was single-arm and dose-escalation only, limiting causal inference. Next steps require a randomized Phase II comparison against temozolomide alone, with central radiographic review and correlative CSF immune profiling to confirm mechanism and durability. Larger manufacturing scale-up is also needed before multicenter testing.