UCFS clinical trial to test efficacy of CAR-T gene therapy against brain tumors

A groundbreaking clinical trial, led by UC San Francisco (UCSF) and funded by a grant of up to $11 million, is expected to revolutionize the treatment for glioblastoma, the most prevalent and lethal adult brain tumor, by using a sophisticated gene therapy known as CAR-T, customized with precision technology.

CAR-T, previously known for its efficacy in extending survival rates among patients battling leukemia and other blood cancers, is undergoing adaptation at UCSF to combat glioblastoma. This enhanced iteration of CAR-T utilizes a cutting-edge technology developed at UCSF dubbed synthetic notch (synNotch), which not only safeguards healthy tissue from harm but also enhances the therapy's effectiveness.

Enrollment for the inaugural clinical trial using this technology commenced this week at UCSF, with a subsequent trial to be conducted in 2025.

Glioblastoma afflicts approximately 12,000 Americans annually, with patients typically surviving a mere 15 months post-diagnosis, underscoring the urgent need for innovative treatments.

Dr. Hideho Okada, a renowned physician-scientist and director of the UCSF Brain Tumor Immunotherapy Center, lauded the initiative as a proof of UCSF's prowess in translational research. The project received substantial funding from the California Institute for Regenerative Medicine (CIRM), with additional support from the National Cancer Institute Specialized Programs of Research Excellence (NCI SPORE).

Dr. Okada says that while the primary objective of the initial phase 1 trial is to ensure safety and evaluate any potential toxicities, the ultimate aim is to significantly extend the lifespan of glioblastoma patients. Preclinical studies in mice have yielded promising results, surpassing expectations and offering hope for a lasting therapeutic solution with minimized side effects, he adds.

Led by principal investigator Dr. Jennifer Clarke, the CIRM-funded trial targets newly diagnosed glioblastoma patients who have completed standard-of-care treatment, provided their tumors exhibit specific mutations identified by the UCSF500 cancer gene panel test. The subsequent study will broaden its scope to include glioblastoma patients irrespective of their genetic profile.

CAR-T therapy involves genetically modifying immune cells extracted from patients to recognize and eradicate cancerous cells. While successful in treating blood cancers, CAR-T has encountered challenges in combating solid tumors like glioblastoma due to tumor cell diversity and the risk of targeting healthy tissue.

To surmount these obstacles, Dr. Okada drew upon the synNotch system developed by Dr. Wendell Lim, which enables precise targeting of tumor-specific antigens while preserving healthy tissue. This innovative approach ensures sustained efficacy against cancer cells while mitigating T-cell exhaustion, a common limitation of conventional CAR-T therapies.

Dr. Lim hailed the breakthrough as a milestone in cancer immunotherapy, likening the engineered CAR-T cells to sophisticated computers capable of making complex decisions based on integrated information.

The ongoing clinical trials at UCSF represent a beacon of hope for glioblastoma patients, offering the promise of extended survival and improved quality of life through pioneering gene therapy approaches.