This month marked an important milestone for UCSF faculty and clinicians working to take on the challenge of glioblastoma multiforme (GBM). They treated their first patient with a promising chimeric antigen receptor (CAR) T-cell therapy that was fully conceived, designed, optimized and manufactured here at UCSF. GBM is the most common and aggressive primary brain tumor with a tremendously poor prognosis of 14-month median survival.
“We are very excited that the first patient in this clinical trial has been dosed with E-SYNC, a cellular therapy designed and manufactured at UCSF that has the potential to change the treatment paradigm for GBM.”
- Alan Ashworth, PhD, FRS, president, UCSF Helen Diller Family Comprehensive Cancer Center
CAR T-cell therapies use a patient’s own T cells - immune cells that find and fight illness and infection in the body - which are removed from the patient, re-programmed to become cancer-seeking and then returned to the body, where they find and destroy the cancer cells. While CAR T-cell therapies have demonstrated long-term remissions in many blood cancers, there are currently no approved, safe and effective CAR T-cell therapies for solid tumors, such as brain cancer. Most antigens found on solid tumor cells, utilized by CAR T-cell therapies, are also found in healthy tissue, leaving the healthy cells open to attack. The CAR T-cell therapy given this month, known as E-SYNC, was designed by Hideho Okada, MD, PhD, and Wendell Lim, PhD, using the SynNotch technology developed in Wendell Lim’s lab which allows E-SYNC to more precisely identify and kill GBM tumor cells, while sparing healthy cells.
The E-SYNC program is part UCSF’s Living Therapeutics Initiative (LTI) which is accelerating the advancement of promising cellular therapies out of the lab and into clinical evaluation. To bring this therapy to patients, the E-SYNC team not only had to tailor the SynNotch technology to address GBM, it also had to overcome the production roadblocks that are challenges with new therapies like E-SYNC. These approaches push the limits of technology and need to use optimized manufacturing processes for clinical scale production to allow clinical delivery for this challenging neuro-oncology indication.
The primary goal of this phase 1 clinical study, led by Jennifer Clarke, MD, MPH, is to evaluate safety and toxicity of this therapy. However, the team will also be evaluating patient outcomes for early signs of efficacy. All the data collected from clinical trial will not only advance the E-SYNC development but also has to potential to inform development of future CAR T-cell therapies.
“We are very excited that the first patient in this clinical trial has been dosed with E-SYNC, a cellular therapy designed and manufactured at UCSF that has the potential to change the treatment paradigm for GBM”, said Alan Ashworth, PhD, FRS, president of the UCSF Helen Diller Family Comprehensive Cancer Center, and director of the Living Therapeutics Initiative.
“The E-SYNC program showcases the breadth and depth of cellular therapy development capabilities at UCSF and is one of a pipeline of innovative cellular therapies that the LTI is advancing towards clinical evaluation.”