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

Autor:	Kekre N; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.; Division of Hematology, Department of Medicine, The Ottawa Hospital, Ottawa, ON, Canada., Hay KA; Division of Hematology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.; Terry Fox Laboratory, British Columbia Cancer Research Institute, Vancouver, BC, Canada.; Vancouver General Hospital, Leukemia and Bone Marrow Transplant Program of British Columbia, Vancouver, BC, Canada., Webb JR; Conconi Family Immunotherapy Lab, Trev and Joyce Deeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, Canada., Mallick R; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada., Balasundaram M; Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Research Institute, Vancouver, BC, Canada., Sigrist MK; Terry Fox Laboratory, British Columbia Cancer Research Institute, Vancouver, BC, Canada., Clement AM; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.; Division of Hematology, Department of Medicine, The Ottawa Hospital, Ottawa, ON, Canada., Nielsen JS; Conconi Family Immunotherapy Lab, Trev and Joyce Deeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, Canada., Quizi J; Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada., Yung E; Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Research Institute, Vancouver, BC, Canada., Brown SD; Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Research Institute, Vancouver, BC, Canada., Dreolini L; Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Research Institute, Vancouver, BC, Canada., Waller DD; Terry Fox Laboratory, British Columbia Cancer Research Institute, Vancouver, BC, Canada., Smazynski J; Conconi Family Immunotherapy Lab, Trev and Joyce Deeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, Canada., Gierc NS; Conconi Family Immunotherapy Lab, Trev and Joyce Deeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, Canada., Loveless BC; Conconi Family Immunotherapy Lab, Trev and Joyce Deeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, Canada., Clark K; Conconi Family Immunotherapy Lab, Trev and Joyce Deeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, Canada., Dyer T; Conconi Family Immunotherapy Lab, Trev and Joyce Deeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, Canada., Hogg R; Conconi Family Immunotherapy Lab, Trev and Joyce Deeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, Canada., McCormick L; Conconi Family Immunotherapy Lab, Trev and Joyce Deeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, Canada., Gignac M; Conconi Family Immunotherapy Lab, Trev and Joyce Deeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, Canada., Bell S; Conconi Family Immunotherapy Lab, Trev and Joyce Deeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, Canada., Chapman DM; Conconi Family Immunotherapy Lab, Trev and Joyce Deeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, Canada., Bond D; Conconi Family Immunotherapy Lab, Trev and Joyce Deeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, Canada., Yong S; Conconi Family Immunotherapy Lab, Trev and Joyce Deeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, Canada., Fung R; Conconi Family Immunotherapy Lab, Trev and Joyce Deeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, Canada., Lockyer HM; Conconi Family Immunotherapy Lab, Trev and Joyce Deeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, Canada., Hodgson V; Conconi Family Immunotherapy Lab, Trev and Joyce Deeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, Canada., Murphy C; Conconi Family Immunotherapy Lab, Trev and Joyce Deeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, Canada., Subramanian A; Conconi Family Immunotherapy Lab, Trev and Joyce Deeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, Canada., Wiebe E; Conconi Family Immunotherapy Lab, Trev and Joyce Deeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, Canada., Yoganathan P; Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada., Medynski L; Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, Canada., Vaillan DC; Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada., Black A; Division of Hematology, Department of Medicine, The Ottawa Hospital, Ottawa, ON, Canada., McDiarmid S; Division of Hematology, Department of Medicine, The Ottawa Hospital, Ottawa, ON, Canada., Kennah M; Division of Hematology, Department of Medicine, The Ottawa Hospital, Ottawa, ON, Canada., Hamelin L; Division of Hematology, Department of Medicine, The Ottawa Hospital, Ottawa, ON, Canada., Song K; Vancouver General Hospital, Leukemia and Bone Marrow Transplant Program of British Columbia, Vancouver, BC, Canada., Narayanan S; Division of Hematology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.; Vancouver General Hospital, Leukemia and Bone Marrow Transplant Program of British Columbia, Vancouver, BC, Canada., Rodrigo JA; Vancouver General Hospital, Leukemia and Bone Marrow Transplant Program of British Columbia, Vancouver, BC, Canada., Dupont S; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada., Hawrysh T; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada., Presseau J; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.; School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada., Thavorn K; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.; School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada., Lalu MM; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada., Fergusson DA; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.; School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada., Bell JC; Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada., Atkins H; Division of Hematology, Department of Medicine, The Ottawa Hospital, Ottawa, ON, Canada.; Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, Canada.; Department of Cellular Molecular Medicine, University of Ottawa, Ottawa, ON, Canada., Nelson BH; Conconi Family Immunotherapy Lab, Trev and Joyce Deeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, Canada.; Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.; Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada., Holt RA; Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Research Institute, Vancouver, BC, Canada.; Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.; Department of Molecular Biology & Biochemistry, Simon Fraser University, Burnaby, BC, Canada.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Dec 19; Vol. 13, pp. 1074740. Date of Electronic Publication: 2022 Dec 19 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.1074740
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Kekre, Hay, Webb, Mallick, Balasundaram, Sigrist, Clement, Nielsen, Quizi, Yung, Brown, Dreolini, Waller, Smazynski, Gierc, Loveless, Clark, Dyer, Hogg, McCormick, Gignac, Bell, Chapman, Bond, Yong, Fung, Lockyer, Hodgson, Murphy, Subramanian, Wiebe, Yoganathan, Medynski, Vaillan, Black, McDiarmid, Kennah, Hamelin, Song, Narayanan, Rodrigo, Dupont, Hawrysh, Presseau, Thavorn, Lalu, Fergusson, Bell, Atkins, Nelson and Holt.)
Databáze:	MEDLINE
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