2022
DOI: 10.3389/fimmu.2022.1074740
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CLIC-01: Manufacture and distribution of non-cryopreserved CAR-T cells for patients with CD19 positive hematologic malignancies

Abstract: 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 rel… Show more

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Cited by 13 publications
(13 citation statements)
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“…Based on the results of the preliminary assessments above, we selected 4 CD22sdCARs (1ug36, 1ug74, 1ug13, and Pas33) for testing in a CAR backbone that has previously been used for CAR delivery in an ongoing CD19 CAR-T clinical trial. 22 , 23 There were several differences between the initial CAR screening plasmid and the clinical trial such as plasmid used, the most significant being a change in the CAR structure from a CD28TM domain to a CD8TM domain (see Figure 3 A). In the CAR-Jurkat assay, CD28TM and CD8TM CAR constructs showed similar responses, although baseline CD69 expression and nonspecific response to Ramos-CD22KO cells were consistently higher with CD8TM CAR-T constructs compared to CD28TM CAR-T constructs ( Figure 3 B).…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…Based on the results of the preliminary assessments above, we selected 4 CD22sdCARs (1ug36, 1ug74, 1ug13, and Pas33) for testing in a CAR backbone that has previously been used for CAR delivery in an ongoing CD19 CAR-T clinical trial. 22 , 23 There were several differences between the initial CAR screening plasmid and the clinical trial such as plasmid used, the most significant being a change in the CAR structure from a CD28TM domain to a CD8TM domain (see Figure 3 A). In the CAR-Jurkat assay, CD28TM and CD8TM CAR constructs showed similar responses, although baseline CD69 expression and nonspecific response to Ramos-CD22KO cells were consistently higher with CD8TM CAR-T constructs compared to CD28TM CAR-T constructs ( Figure 3 B).…”
Section: Resultsmentioning
confidence: 99%
“…To identify a lead CD22sdCAR construct, we next performed a functional comparison of the 4 CD8TM-CD22sdCAR candidate molecules implementing full-sample randomization and blinding and using a CAR-T production process mimicking the cell manufacturing approach for an ongoing CD19 CAR-T clinical trial. 22 CAR-T products were generated and characterized (see Table S2 ) before being cryopreserved, anonymized, and transferred to a separate site for in vitro and in vivo testing. Consistent with the results above, in vitro functional testing showed highly similar CD22-specific repression of target cell growth across all constructs ( Figures S7 A–S7F).…”
Section: Resultsmentioning
confidence: 99%
“…D) Autologous/allogeneic TILs vs. autologous wildtype (WT) or MHCI-deficient ( B2M - ) tumour. E) CD19-specific CAR-T 27 or non-transduced T-cells vs. CD19+ Daudi target cells.…”
Section: Detection Of Effective Target Cell Killersmentioning
confidence: 99%
“…All procedures were approved by the Ethics Committee of the Capital Region of Denmark and national regulations for biomedical research (Ethical approval reference: H-20070020; Data Protection approval P-2021-303). The CD19-specific CAR-T cell construct 27 was generously provided by the Holt group at the BC Cancer Research Institute (Vancouver, Canada). Biorender.com, GraphPad Prism v10 (GraphPad Software, Boston, Massachusetts, USA), and FlowJo™ v10.0 Software (BD Life Sciences, Ashland, Oregon, USA) were used for figure generation.…”
Section: Acknowledgmentsmentioning
confidence: 99%
“…This has been done in Spain, for example [ 27 , 28 ]. In Canada, the ExCELLirate Canada Platform and the CLIC (Canadian Led Immunotherapies in Cancer) program are also working toward Canadian-made CAR-T products within the academic setting, which will hopefully prove to be cheaper than but equally effective as existing commercial products [ 29 ]. This could be a game-changer for the economic impact of CAR-T cells, assuming the incidence and severity related to adverse events with this manufacturing model are unchanged.…”
Section: Reduction In Costs Of Car-t Cellsmentioning
confidence: 99%