Breaking Barriers in Brain Cancer: PHASE ONE Funds Innovative CAR T Cell Immunotherapy for Glioblastoma

PHASE ONE Foundation has awarded a $300,000 Medical Grant to support a pioneering clinical trial led by Dr. Christine Brown at City of Hope, a national cancer research and treatment organization. The clinical trial aims to transform treatment for glioblastoma, one of the most aggressive and lethal forms of brain cancer. 

Glioblastoma is a profoundly destructive disease with an urgent need for new therapies. It grows fast, infiltrates healthy brain tissue, and is notoriously resistant to conventional treatments such as surgery, radiation, and chemotherapy. Most patients live only 12 to 24 months after diagnosis. Fewer than 10 percent survive five years. 

This new study is designed to change that trajectory. It focuses on a highly innovative approach called CAR T cell therapy, which reprograms a patient’s own immune cells to recognize and attack cancer. While CAR T therapies have already revolutionized the treatment of certain leukemias and lymphomas, applying them to solid tumors like brain cancers has proven far more complex. Glioblastoma creates an intensely hostile microenvironment, rich in molecules that actively suppress immune responses and help the tumor evade attack. 

One of the key culprits is a signaling molecule called TGFβ (transforming growth factor beta). In the context of glioblastoma, TGFβ acts like a powerful “off switch” for immune cells, blunting their ability to function just when they are needed most. That is where this trial breaks new ground. 

In prior early‑phase clinical work, Dr. Brown’s group at City of Hope tested CAR T cells that target a protein called IL13Rα2, which is commonly found on glioblastoma cells but largely absent from normal brain tissue. Those trials demonstrated that IL13Rα2‑directed CAR T cells could be delivered safely to the brain and, in some patients, led to dramatic tumor regressions. One individual has remained in complete remission for six years without additional therapy. However, many patients eventually experienced tumor recurrence, underscoring the need to make these therapies more durable and resilient. 

The new PHASE ONE–funded trial builds directly on that foundation. Using advanced gene‑editing technology (CRISPR‑Cas9), Dr. Brown’s team will engineer CAR T cells that not only target IL13Rα2 but are also rendered resistant to TGFβ. By knocking out the gene for the TGFβreceptor (TGFβR2), the modified T cells are designed to ignore the tumor’s suppressive “stand down” signal and remain active in the hostile environment of the brain. 

The treatment process follows a carefully coordinated sequence. Patients with recurrent glioblastoma or related high‑grade gliomas whose tumors express IL13Rα2 will have their white blood cells collected through a standard procedure called leukapheresis. In the laboratory, these T cells are activated, outfitted with a chimeric antigen receptor (CAR) that recognizes IL13Rα2, and gene‑edited to remove the TGFβR2 receptor. The resulting TGFβ‑resistant CAR T cells are then expanded to clinical scale under rigorous manufacturing conditions. 

After cell preparation, patients undergo surgery to remove as much of the tumor as safely possible. During that procedure, they’ll place specialized catheters into the tumor cavity and/or the cerebrospinal fluid spaces. Rather than infusing CAR T cells intravenously, the team delivers them directly into the brain through these catheters in weekly treatments— a precision strategy that places the therapy exactly where it is needed and bypasses many of the barriers that limit systemic therapies. 

The primary goals of this Phase I trial are to assess safety, determine the optimal dose, and evaluate feasibility of this complex, next‑generation CAR T manufacturing and delivery approach. Investigators will also track early signs of clinical benefit, including tumor responses on MRI scans and patient survival at three, six, and nine months. 

“Our team is incredibly grateful for PHASE ONE’s vision and partnership, allowing us to bring this first-in-human, gene-edited CAR T cell therapy to patients with otherwise incurable brain tumors. By engineering CAR T cells to both eliminate tumor cells and resist the hostile immunosuppressive environment, we hope this new approach will lead to improved outcomes for patients.” –Christine Brown, PhD, Heritage Provider Network Professor in Immunotherapy, City of Hope 

This study directly aligns with PHASE ONE’s mission: to fund early, high‑impact cancer research that can move quickly from concept to the clinic. By supporting this first‑in‑human trial, PHASE ONE is catalyzing a bold step forward in the fight against one of the most devastating cancers patients and families can face. 

“Dr. Brown's research strives to bring CAR-T immunotherapy to glioblastoma, with the promise of prolonging life and eradicating cancer with the most cutting-edge biotechnology. This is exactly the sort of research that is only possible with grants like those from PHASE ONE.” –Adam Braun, MD, PHASE ONE Medical Advisory Board 

For patients with recurrent glioblastoma, time is precious. This collaboration between PHASE ONE and City of Hope seeks to convert cutting‑edge science into tangible hope— not in the distant future, but in the next wave of clinical care.