Brain Cancer Chromosomes. Image courtesy NCI Center for Cancer Research
Glioblastoma is the most common malignant brain tumor and among the most treatment-resistant cancers. In the last 15 years, numerous attempts to develop new drugs for glioblastoma have failed.
In response, the National Cancer Institute (NCI) has established the Glioblastoma Therapeutics Network (GTN) to support discovery and development of novel therapeutics for glioblastoma. UCSF is among the five teams selected to join the GTN, receiving an award of $4.2M to aid drug discovery and early clinical studies.
Co-led by Nicholas Butowski, MD (Professor of Neurological Surgery at UCSF) and Roger Stupp, MD (Professor of Neurological Surgery, Neurology, and Medicine at Northwestern University), the multi-institution team comprises clinicians and researchers from UCSF Brain Tumor Center and the Robert H. Lurie Comprehensive Cancer Center. Collectively, the collaborators will concentrate their efforts on two projects – both of which are innovative immunotherapy clinical trials for patients with glioblastoma.
“We are honored to partner with the NCI and the team from Northwestern and are excited to develop meaningful and effective immunotherapy options for patients with glioblastoma,” said Butowski. “We also look forward to working with the institutions in the other GTN teams to expand therapeutic options for our patients in other realms, including small molecule and targeted approaches.”
Addressing Key Challenges of Immunotherapy
The first project supported by the NCI grant will be led by Adam Sonabend Worthalter, MD (Assistant Professor of Neurological Surgery at Northwestern University).
Despite successful preclinical results, various immunotherapies have failed to improve outcomes for patients with glioblastoma. Existing challenges include tumor microenvironments that are typically immunosuppressive, along with insufficient penetration of the drug across the blood-brain barrier.
Sonabend Worthalter and colleagues seek to address these limitations in a new phase I clinical trial for glioblastoma. The study will evaluate a novel immunotherapy drug in combination with an immune sensitizing agent, together with an ultrasound-based therapy to open the blood-brain barrier.
Stupp will co-lead the project, alongside Hui Zhang, PhD (Professor of Preventative Medicine at Northwestern University).
Developing a New Class of Therapeutic Agents
The second project supported by the NCI grant will be led by immunotherapy expert Hideho Okada, MD, PhD (Professor of Neurological Surgery at UCSF).
Previous immunotherapies, like traditional CAR T cells, were ineffective at preventing recurrence. They could only target a portion of the cancer cells, leaving some cells to continue proliferating.