CLIC-01：CD19 阳性血液恶性肿瘤患者非冷冻保存 CAR-T 细胞的制备和分发

UNLABELLED: 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 6 CAR-T cells/kg (range 0. 13-3. 6 10 6 /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 REGISTRATION: https://clinicaltrials. gov/ct2/show/NCT03765177, identifier NCT03765177.