Point-Of-Care CAR T-Cell Production (ARI-0001) Using a Closed Semi-automatic Bioreactor: Experience From an Academic Phase I Clinical Trial.

Frontiers in Immunology
Maria CastellaManel Juan

Abstract

Development of semi-automated devices that can reduce the hands-on time and standardize the production of clinical-grade CAR T-cells, such as CliniMACS Prodigy from Miltenyi, is key to facilitate the development of CAR T-cell therapies, especially in academic institutions. However, the feasibility of manufacturing CAR T-cell products from heavily pre-treated patients with this system has not been demonstrated yet. Here we report and characterize the production of 28 CAR T-cell products in the context of a phase I clinical trial for CD19+ B-cell malignancies (NCT03144583). The system includes CD4-CD8 cell selection, lentiviral transduction and T-cell expansion using IL-7/IL-15. Twenty-seven out of 28 CAR T-cell products manufactured met the full list of specifications and were considered valid products. Ex vivo cell expansion lasted an average of 8.5 days and had a mean transduction rate of 30.6 ± 13.44%. All products obtained presented cytotoxic activity against CD19+ cells and were proficient in the secretion of pro-inflammatory cytokines. Expansion kinetics was slower in patient's cells compared to healthy donor's cells. However, product potency was comparable. CAR T-cell subset phenotype was highly variable among patients an...Continue Reading

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Citations

Oct 4, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Valentín Ortíz-MaldonadoJulio Delgado
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Sep 4, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Samanta Romina ZanettiPablo Menéndez

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Methods Mentioned

BETA
density gradient centrifugation
flow cytometry
PCR
FACS

Clinical Trials Mentioned

NCT03144583

Software Mentioned

CliniMACS Prodigy
R
Prodigy
DB
FlowJo

Related Concepts

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Bioreactors (ASM)

Bioreactors are important devices or systems that utilize living cells or enzymes for a chemical process. These devices carefully control and monitor the environment factors such as pH, nutrients level, and temperature, which can affect the yield in a given process. Discover the latest research here.