使用 CliniMACS Prodigy 床旁生产抗 CD19.1 CAR-T 细胞：来自约旦的真实世界经验

Industry-driven chimeric antigen receptor (CAR)-T cell manufacturing is complex and time-consuming. We hypothesized that decentralized manufacturing of CAR-T cells on an automated closed CliniMACS Prodigy system (Miltenyi Biotec) is feasible and reproducible for patients with relapsed refractory non-Hodgkin's lymphoma (rrNHL) in a developing country.

To manufacture anti-MB-19.1-CAR-T cell products, peripheral blood mononuclear cells were collected, enriched into pure T cells by positive selection using CD4 and CD8 magnetic beads, redirected into the chamber of the CliniMACS Prodigy for activation with the T-cell TransAct reagent containing CD3 and CD28, followed by transduction by anti-MB-CD19.1-CAR Lentiviral Vector, and cultured for 12 days followed by cell harvesting. Eleven products were manufactured, three from healthy donors for feasibility evaluation and eight clinical-grade products under a phase II clinical trial. Quality control and release manufacturer standards were set to ensure their identity, viability, purity, sterility, and potency.

Eleven anti-CD19.1-CAR-T products with reproducible key characteristics were manufactured. Validation run data demonstrated a successful anti-CD19.1-CAR-T cell production with 51-fold T-cell expansion, a robust transduction efficiency of 26%, a viability of 98%, and fulfillment of manufacturer standards for clinical application. Clinical-grade products demonstrated 35-fold T-cell expansion, 44% transduction efficiency, and 99.8% viability, and fulfilling quality checks. The average vein-to-vein time is 15.25 days (range, 15-17). Safety and efficacy of clinical-grade products in the first eight patients enrolled showed reasonable objective responses with no new safety signals.

Our data highlight the feasibility and reproducibility of the point of care of anti-CD19.1-CAR-T cells in a developing country, Jordan.