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Kekre, Natasha; Hay, Kevin A.; Webb, John R.; Mallick, Ranjeeta; Balasundaram, Miruna; Sigrist, Mhairi K.; Clement, Anne-Marie; Nielsen, Julie S.; Quizi, Jennifer; Yung, Eric; Brown, Scott D.; Dreolini, Lisa; Waller, Daniel D.; Smazynski, Julian; Gierc, Nicole S.; Loveless, Bianca C.; Clark, Kayla; Dyer, Tyler; Hogg, Richard; McCormick, Leah; Gignac, Michael; Bell, Shanti; Chapman, D. Maria; Bond, David; [...]

CLIC-01: Manufacture and distribution of non-cryopreserved CAR-T cells for patients with CD19 positive hematologic malignancies

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  • Medientyp: E-Artikel
  • Titel: CLIC-01: Manufacture and distribution of non-cryopreserved CAR-T cells for patients with CD19 positive hematologic malignancies
  • Beteiligte: Kekre, Natasha; Hay, Kevin A.; Webb, John R.; Mallick, Ranjeeta; Balasundaram, Miruna; Sigrist, Mhairi K.; Clement, Anne-Marie; Nielsen, Julie S.; Quizi, Jennifer; Yung, Eric; Brown, Scott D.; Dreolini, Lisa; Waller, Daniel D.; Smazynski, Julian; Gierc, Nicole S.; Loveless, Bianca C.; Clark, Kayla; Dyer, Tyler; Hogg, Richard; McCormick, Leah; Gignac, Michael; Bell, Shanti; Chapman, D. Maria; Bond, David; [...]
  • Erschienen: Frontiers Media SA, 2022
  • Erschienen in: Frontiers in Immunology
  • Sprache: Nicht zu entscheiden
  • DOI: 10.3389/fimmu.2022.1074740
  • ISSN: 1664-3224
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:p>Access to commercial CD19 CAR-T cells remains limited even in wealthy countries like Canada due to clinical, logistical, and financial barriers related to centrally manufactured products. We created a non-commercial academic platform for end-to-end manufacturing of CAR-T cells within Canada’s publicly funded healthcare system. We report initial results from a single-arm, open-label study to determine the safety and efficacy of in-house manufactured CD19 CAR-T cells (entitled CLIC-1901) in participants with relapsed/refractory CD19 positive hematologic malignancies. Using a GMP compliant semi-automated, closed process on the Miltenyi Prodigy, T cells were transduced with lentiviral vector bearing a 4-1BB anti-CD19 CAR transgene and expanded. Participants underwent lymphodepletion with fludarabine and cyclophosphamide, followed by infusion of non-cryopreserved CAR-T cells. Thirty participants with non-Hodgkin’s lymphoma (n=25) or acute lymphoblastic leukemia (n=5) were infused with CLIC-1901: 21 males (70%), median age 66 (range 18-75). Time from enrollment to CLIC-1901 infusion was a median of 20 days (range 15-48). The median CLIC-1901 dose infused was 2.3 × 10<jats:sup>6</jats:sup> CAR-T cells/kg (range 0.13-3.6 × 10<jats:sup>6</jats:sup>/kg). Toxicity included ≥ grade 3 cytokine release syndrome (n=2) and neurotoxicity (n=1). Median follow-up was 6.5 months. Overall response rate at day 28 was 76.7%. Median progression-free and overall survival was 6 months (95%CI 3-not estimable) and 11 months (95% 6.6-not estimable), respectively. This is the first trial of in-house manufactured CAR-T cells in Canada and demonstrates that administering fresh CLIC-1901 product is fast, safe, and efficacious. Our experience may provide helpful guidance for other jurisdictions seeking to create feasible and sustainable CAR-T cell programs in research-oriented yet resource-constrained settings.</jats:p><jats:sec><jats:title>Clinical trial registration</jats:title><jats:p><jats:uri>https://clinicaltrials.gov/ct2/show/NCT03765177</jats:uri>, identifier NCT03765177.</jats:p></jats:sec>
  • Zugangsstatus: Freier Zugang