Frontiers in Immunology (Dec 2022)

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

  • Natasha Kekre,
  • Natasha Kekre,
  • Kevin A. Hay,
  • Kevin A. Hay,
  • Kevin A. Hay,
  • John R. Webb,
  • Ranjeeta Mallick,
  • Miruna Balasundaram,
  • Mhairi K. Sigrist,
  • Anne-Marie Clement,
  • Anne-Marie Clement,
  • Julie S. Nielsen,
  • Jennifer Quizi,
  • Jennifer Quizi,
  • Eric Yung,
  • Scott D. Brown,
  • Lisa Dreolini,
  • Daniel D. Waller,
  • Julian Smazynski,
  • Nicole S. Gierc,
  • Bianca C. Loveless,
  • Kayla Clark,
  • Tyler Dyer,
  • Richard Hogg,
  • Leah McCormick,
  • Michael Gignac,
  • Shanti Bell,
  • D. Maria Chapman,
  • David Bond,
  • Siao Yong,
  • Rachel Fung,
  • Heather M. Lockyer,
  • Victoria Hodgson,
  • Catherine Murphy,
  • Ana Subramanian,
  • Evelyn Wiebe,
  • Piriya Yoganathan,
  • Piriya Yoganathan,
  • Liana Medynski,
  • Dominique C. Vaillan,
  • Dominique C. Vaillan,
  • Alice Black,
  • Sheryl McDiarmid,
  • Michael Kennah,
  • Linda Hamelin,
  • Kevin Song,
  • Sujaatha Narayanan,
  • Sujaatha Narayanan,
  • Judith A. Rodrigo,
  • Stefany Dupont,
  • Terry Hawrysh,
  • Justin Presseau,
  • Justin Presseau,
  • Kednapa Thavorn,
  • Kednapa Thavorn,
  • Manoj M. Lalu,
  • Dean A. Fergusson,
  • Dean A. Fergusson,
  • John C. Bell,
  • John C. Bell,
  • Harold Atkins,
  • Harold Atkins,
  • Harold Atkins,
  • Brad H. Nelson,
  • Brad H. Nelson,
  • Brad H. Nelson,
  • Robert A. Holt,
  • Robert A. Holt,
  • Robert A. Holt

DOI
https://doi.org/10.3389/fimmu.2022.1074740
Journal volume & issue
Vol. 13

Abstract

Read online

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 × 106 CAR-T cells/kg (range 0.13-3.6 × 106/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.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03765177, identifier NCT03765177.

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