A phase I clinical trial showed that patients with newly diagnosed glioblastoma who received multiple doses of genetically modified immune cells directly into the brain lived twice as long without cancer progression compared to those given a single dose.
The treatment, called drug-resistant immunotherapy (DRI), collects gamma-delta T cells from the patient, modifies them in a lab to resist the chemotherapy drug temozolomide, and delivers them into the tumor cavity through a small tube placed during surgery.
Survival outcomes
Participants who received repeated injections of DRI cells had a median progression-free survival of 16.1 months, while those who received only one dose reached 8 months. The median progression-free survival for all 13 participants was 9.9 months.
The median overall survival for all treated patients was 15.6 months, with a range of 5 to 51 months. Single-dose recipients had a median overall survival of 15.6 months, while those given multiple doses reached 19.5 months. Several patients remained alive and progression-free when data collection concluded.
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The team noted stronger and longer-lasting recovery of T cells and natural killer cells in the blood of patients who received more doses, even during chemotherapy, which usually weakens immune function.
Trial structure and patient details
The study used a modified 3+3 frequency-escalation design, increasing the number of doses rather than the cell count per dose. Each injection contained 1 × 10⁷ DRI cells. The first cohort received one dose, the second up to three, and the third up to six.
Of 23 people assessed, 13 received the treatment. The group was 62% male, with a median age of 66. Most had IDH wild-type tumors, while 54% had MGMT-unmethylated tumors, a marker tied to worse outcomes. Nearly half underwent subtotal resection, leaving some tumor behind after surgery.
Surgery placed a small catheter into the tumor cavity. After recovery, patients underwent apheresis to collect immune cells. These cells were modified in a bioreactor with an MGMT-expressing gene, allowing them to survive temozolomide. The modified cells were stored until use.
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During each chemotherapy cycle, patients first received 150 mg/m² of temozolomide intravenously. Within four hours, the DRI cells were thawed and injected through the catheter. Patients were monitored in an outpatient clinic before continuing oral temozolomide for four more days.
Five patients did not receive the therapy because their cells failed quality checks. Four withdrew consent, and one did not complete initial chemotherapy and radiation. The trial took place at a single center and was funded by IN8bio, Inc.
Side effects observed
No dose-limiting toxicities occurred, and no cases of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome were reported.
Grade 3 side effects included decreased platelet count, decreased white blood cell count, deep vein thrombosis, and hypertension. Grade 4 events were rare, with decreased neutrophil count and pulmonary embolism each reported in a small percentage of patients.
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Blood samples were tested for replication-competent lentivirus at multiple points up to a year after treatment. All results came back negative. Serum protein analysis also found no significant increases in inflammatory markers tied to cytokine release syndrome.
The results appeared in the Journal of Clinical Oncology, led by Dr. Louis B. Nabors.
This approach could offer new hope for patients facing limited options.
