CAR-T Cells Successfully Manufactured at Point-of-Care

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.

Reference

1. 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.