Cells produced by this method were also shown to be more potent in animal models than cells made with typical processes.
A new manufacturing process developed by investigators at University Hospitals (UH) Seidman Cancer Center in collaboration with a biotech start-up company could reduce the time to manufacture chimeric antigen receptor T-cell (CAR-T) therapies to approximately 24 hours.
The timeframe is substantially shorter than both the investigators’ previous benchmark of 8 days and typical commercial manufacturing times, which often are about 3 weeks. In addition to the faster manufacturing time, the cells produced by this method were also shown to be more potent in animal models than cells made with typical processes. The new process will be tested in a phase 1 clinical trial (NCT05400109) with UF-KURE19 CAR-T cells for patients with relapsed/refractory (r/r) non-Hodgkin lymphomas. However, the investigators expressed optimism that the process could eventually be tested for patients with other types of cancers as well.
“Some patients just don't have a lot of time, so streamlining this manufacturing process and potentially even making a more effective product is very important and will ultimately benefit a lot of people,” James Martin, MD, UH Seidman Cancer Center, who is the principal investigator of the trial, said in a statement regarding the news.
The single-arm, open-label, dose-escalation study will enroll approximately 10 participants aged 18 years or older who have been diagnosed with CD19 positive non-Hodgkin lymphoma that is relapsed after at least 2 lines of therapy or refractory to chemotherapy. Participants are required to have an Eastern Cooperative Oncology Group Performance status of at least 2, a total bilirubin less than or equal to 2.5X the institutional upper limit of normal, a calculated creatinine clearance of at least 30 mL/min, a cardiac ejection fraction of at least 45% with no evidence of pericardial effusion, and adequate pulmonary function. Patients with myelodysplasia or cytogenetic abnormality indicative of myelodysplasia; active central nervous system or meningeal involvement by lymphoma; or untreated brain metastases or central nervous system disease will be excluded from the trial. Additional exclusion criteria relate to patient health status and treatment history.
Participants will be administered 30 mg/m2/IV of fludarabine and 500 mg/m2/IV of cyclophosphamide before receiving UF-KURE19 CAR-T cells at their assigned dose level. The study’s primary end points include the recommended maximum tolerated dose (MTD) of UF-KURE19 and the toxicities associated with the MTD. Secondary end points include the rate of manufacture success, the incidence of treatment-emergent adverse events (AEs), overall response, progression-free survival, and overall survival. The study is being carried out with the collaboration of the Case Comprehensive Cancer Center at Case Western Reserve University and Cleveland Clinic. It is estimated to be completed in December 2026.
“We're trying to do this, eventually, as a therapy that can be manufactured outside of a specialized Good Manufacturing Practice (GMP) lab so that it could be more amenable to most major hospitals around the world, especially in places and other countries where they don't have a lot of this sophisticated expertise and facilities currently needed to manufacture CAR T-cells themselves,” David Wald, MD, PhD, associate director for Basic Research, Wesley Center for Immunotherapy at UH Seidman Cancer Center, and associate professor of Pathology, Case Western Reserve University School of Medicine, added to the statement. “The goal is to create a very simple, one-day process that doesn't need a lot of complex equipment or expertise.”