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Optimisation of a primary human CAR-NK cell manufacturing pipeline.

التفاصيل البيبلوغرافية
العنوان: Optimisation of a primary human CAR-NK cell manufacturing pipeline.
المؤلفون: Pfefferle A; Biomedicine Discovery Institute and the Department of Biochemistry and Molecular Biology Monash University Clayton VIC Australia.; oNKo-Innate Pty Ltd Moonee Ponds VIC Australia., Contet J; oNKo-Innate Pty Ltd Moonee Ponds VIC Australia., Wong K; oNKo-Innate Pty Ltd Moonee Ponds VIC Australia., Chen C; oNKo-Innate Pty Ltd Moonee Ponds VIC Australia., Verhoeyen E; CIRI, Université de Lyon, INSERM U1111, ENS de Lyon Université Lyon 1, CNRS, UMR 5308 Lyon France.; INSERM, C3M Université Côte d'Azur Nice France., Slichter CK; Kite Pharma, a Gilead Company Santa Monica CA USA., Schluns KS; Kite Pharma, a Gilead Company Santa Monica CA USA., Cursons J; oNKo-Innate Pty Ltd Moonee Ponds VIC Australia., Berry R; oNKo-Innate Pty Ltd Moonee Ponds VIC Australia., Nikolic I; oNKo-Innate Pty Ltd Moonee Ponds VIC Australia., Rautela J; Biomedicine Discovery Institute and the Department of Biochemistry and Molecular Biology Monash University Clayton VIC Australia.; oNKo-Innate Pty Ltd Moonee Ponds VIC Australia., Huntington ND; Biomedicine Discovery Institute and the Department of Biochemistry and Molecular Biology Monash University Clayton VIC Australia.; oNKo-Innate Pty Ltd Moonee Ponds VIC Australia.
المصدر: Clinical & translational immunology [Clin Transl Immunology] 2024 May 02; Vol. 13 (5), pp. e1507. Date of Electronic Publication: 2024 May 02 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: John Wiley & Sons Australia, Ltd. on behalf of Australasian Society for Immunology Inc Country of Publication: Australia NLM ID: 101638268 Publication Model: eCollection Cited Medium: Print ISSN: 2050-0068 (Print) Linking ISSN: 20500068 NLM ISO Abbreviation: Clin Transl Immunology Subsets: PubMed not MEDLINE
أسماء مطبوعة: Publication: 2018- : [Milton, Queensland] : John Wiley & Sons Australia, Ltd. on behalf of Australasian Society for Immunology Inc.
Original Publication: [London] : Nature Publishing Group, 2012-
مستخلص: Objectives: Autologous chimeric antigen receptor (CAR) T-cell therapy of B-cell malignancies achieves long-term disease remission in a high fraction of patients and has triggered intense research into translating this successful approach into additional cancer types. However, the complex logistics involved in autologous CAR-T manufacturing, the compromised fitness of patient-derived T cells, the high rates of serious toxicities and the overall cost involved with product manufacturing and hospitalisation have driven innovation to overcome such hurdles. One alternative approach is the use of allogeneic natural killer (NK) cells as a source for CAR-NK cell therapy. However, this source has traditionally faced numerous manufacturing challenges.
Methods: To address this, we have developed an optimised expansion and transduction protocol for primary human NK cells primed for manufacturing scaling and clinical evaluation. We have performed an in-depth comparison of primary human NK cell sources as a starting material by characterising their phenotype, functionality, expansion potential and transduction efficiency at crucial timepoints of our CAR-NK manufacturing pipeline.
Results: We identified adult peripheral blood-derived NK cells to be the superior source for generating a CAR-NK cell product because of a higher maximum yield of CAR-expressing NK cells combined with potent natural, as well as CAR-mediated anti-tumor effector functions.
Conclusions: Our optimised manufacturing pipeline dramatically improves lentiviral transduction efficiency of primary human NK cells. We conclude that the exponential expansion pre- and post-transduction and high on-target cytotoxicity make peripheral blood-derived NK cells a feasible and attractive CAR-NK cell product for clinical utility.
Competing Interests: JC, RB and IN report employment with oNKo‐Innate. NDH, JR, IN, JC and RB report stock or other ownership in oNKo‐Innate. NDH serves on an advisory board for Bristol Myers Squibb and Syena. CKS and KSS report employment with Kite, a Gilead company, and stock or other ownership in Gilead Sciences. KSS serves on the advisor board of Obsidian Therapeutics.
(© 2024 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)
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فهرسة مساهمة: Keywords: NK cells; immunotherapy; lymphocytes; translational immunology
تواريخ الأحداث: Date Created: 20240506 Latest Revision: 20240507
رمز التحديث: 20240507
مُعرف محوري في PubMed: PMC11063921
DOI: 10.1002/cti2.1507
PMID: 38707997
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-0068
DOI:10.1002/cti2.1507