Dr Choi on the Importance of Education on CAR T-Cell Therapy Manufacturing in Hematologic Malignancies

When developing our operating model, we always consider people, process, and technology. Being based at an academic institution gives us the unique opportunity to closely examine both the manufacturing process and the final product, allowing us to better understand the sources of variability between donors and patients."

Yeong “Christopher” Choi, PhD, MBA, the senior vice president of Industry Partnerships, associate professor of oncology in the Department of Medicine, and technical director of the GMP Facility in the Center for Immunotherapy at Roswell Park Comprehensive Cancer Center, discussed the importance of comprehensive product and process education to mitigate variability in CAR T-cell therapy manufacturing and improve treatment outcomes for patients with hematologic malignancies.

In the early phases of testing for new CAR T-cell therapies under development, the primary objective is to assess safety and determine preliminary efficacy signals, Choi explained. However, as therapies move into phase 2 and approach potential regulatory filings for regulatory approval, consistency in manufacturing becomes paramount, Choi said. The shift in focus from early-phase exploratory goals to late-phase reproducibility reflects the increasing need for standardization across the therapeutic development lifecycle.

Despite advances in biomanufacturing technology, biologic variability remains a critical challenge, Choi noted. The primary driver of this variability is the source material derived from the patient in cases of autologous products or donors for allogeneic products. Differences in immune cell phenotypes and functionality can influence the expansion and quality of the CAR T-cell product, highlighting the need for a more refined understanding of both the product and the manufacturing process, Choi explained.

At Roswell Park, this challenge is approached through a framework centered on people, process, and technology. The academic setting allows for close examination of each component of the CAR T-cell manufacturing workflow, enabling continuous improvement and optimization. According to Choi, educating stakeholders across disciplines—manufacturing staff, clinicians, and researchers—about the factors influencing variability in manufacturing is essential for scaling CAR T-cell therapies with maintained quality and efficacy.

This focus on education supports better decision-making throughout the clinical trial and commercial development processes, ensuring that product variability is addressed proactively rather than retrospectively. Choi concluded by noting that a deeper understanding of donor- and patient-driven variability is necessary to refine cell therapy platforms and successfully integrate them into clinical practice.