|The following article features coverage from the American Society of Hematology (ASH) 2018 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Chimeric antigen receptor T (CAR-T) cells targeted to CD19 and CD20 were successfully generated at the point-of-care using a good manufacturing practice-compliant closed system, according to data presented at the 2018 American Society of Hematology (ASH) Annual Meeting and Exposition.1
The authors stated that the study “successfully demonstrated feasibility for point-of-care CAR-T cell production for clinical use from patient apheresis products utilizing the CliniMACS Prodigy device.”
The US Food and Drug Administration has approved 2 CAR-T products to date, but commercial CAR-T products are limited by the length of time of off-site production, which can also restrict use in rapidly progressing patients, and high cost. The purpose of this phase 1 trial was to determine if CAR-T cells could be generated at the point-of-care.
The study used the CliniMACS Prodigy device to manufacture CAR-T cells at the Medical College of Wisconsin Cell Therapy Laboratory. Peripheral blood mononuclear cells were collected by apheresis and loaded into the Prodigy device to enrich CD4 and CD8 T cells. T cells were then cultured and stimulated, followed by transfection with lentiviral vectors expressing anti-CD19 and anti-CD20 with CD3ζ and 4-1BB stimulatory domains. The final products were harvested on day 14, and expression of CD20.19 CAR was assessed by protein L staining.
The ongoing trial has successfully generated CAR-T cells for all 6 currently enrolled patients, with no production failures. The mean CD20.19 expression was 20.8%, and the generated CAR-T cells demonstrated killing of CD19+ and CD20+ target cells in vitro and secreted interferon-gamma in response to the target cells.
The CAR-T cell yield was higher than what was required for dosing, at a mean of 5.9e + 8 (range, 4.3-7.9e + 8), and the CAR-T cells included by CD4 and CD8 cells that were primarily of an effector-memory phenotype (82%).
Though harvesting was performed on day 14, in-process testing demonstrated that sufficient numbers of CAR-T cells were available on day 8.
The authors concluded that these data indicate that generation of CAR-T cells at the point-of-care was efficient and reproducible, though the processing time could be reduced. They noted that “a major clinical advantage of CAR-T cells generated on-site is the flexibility in treatment.”
Read more of Cancer Therapy Advisor‘s coverage of the ASH 2018 meeting by visiting the conference page.
- Zhu F, Shah NN, Schneider D, et al. Point-of-care manufacturing of CD20.19 bi-specific chimeric antigen receptor T (CAR-T) cells in a standard academic cell processing facility for a phase I clinical trial in relapsed, refractory NHL. Poster presentation at: American Society of Hematology 60th Annual Meeting and Exposition; December 1-4, 2018; San Diego, CA. Abstract 4553.