Groundbreaking Dual‑Target CAR‑T Therapy Shows Promise in Recurrent Glioblastoma

For two decades, glioblastoma multiforme (GBM), the most aggressive primary brain cancer, has defied major therapeutic advances. However, a recent Phase I trial, combining Gilead Sciences' Kite unit and University of Pennsylvania, marks a breakthrough. A dual‑target CAR‑T therapy, administered directly into cerebrospinal fluid, achieved tumor shrinkage in 62% of recurrent GBM patients—unusual for such a resilient cancer Reuters+10Reuters+10Larvol Delta+10.

Mechanism & Innovation

Unlike conventional therapies focusing on a single antigen, this dual-target approach neutralizes:

• EGFR (expressed in ~50–60% of GBM cases),
  
  
• IL‑13Rα2 (found in ~75%)
  
  

This strategy addresses tumor heterogeneity, a major barrier to efficacy in solid tumors MedPathFrontiers. The CAR‑T cells, engineered from the patient’s own T‑cells, are delivered intrathecally—directly to the tumor’s environment—bypassing the blood-brain barrier and promoting more effective targeting Cell+14ecancer+14Reuters+14.

Clinical Findings

• Trial included 18 recurrent GBM patients, 13 had measurable tumors.
  
  
• 62% (8/13) showed significant tumor shrinkage Newsroom+11Reuters+11Larvol Delta+11Penn Today+5ecancer+5The ASCO Post+5.
  
  
• 11% remained disease-stable beyond 6 months; 43% survived past 12 months, a stark improvement against the usual 6–10‑month prognosis Larvol Delta+9ecancer+9MedPath+9.
  
  
• One patient exhibited 16 months of stable disease MDPI+12Reuters+12MedPath+12.
  
  

These results were discussed at ASCO 2025 and published in Nature Medicine STAT+10Reuters+10Penn Today+10.

Safety & Future Directions

• Adverse events (Grade 3 neurotoxicity) occurred in ~56%, but were manageable within clinical protocols The ASCO Post+3ecancer+3MedPath+3.
  
  
• An upcoming cohort will receive multiple doses to improve durability and response.
  
  
• Plans are underway to evaluate this therapy in newly diagnosed GBM patients, where early intervention could enhance outcomes MedPath+14ecancer+14MedPath+14.
  
  

Why It Matters

1. Addresses Solid Tumor Hurdles
   Dual-target design and intrathecal delivery overcome key challenges: tumor diversity and BBB penetration—issues that stymie CAR-T therapies in solid cancers MedPath+2ecancer+2Penn Today+2MedPath.
   
   
2. Promising Survival Signals
   Nearly half of patients exceeded 12 months survival—significantly above historical norms MedPath+1Reuters+1Penn Today+3ecancer+3The ASCO Post+3.
   
   

Blueprint for Broader Application
If validated in larger trials, this method could become a model for CAR‑T against other resistant solid tumors.