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Cited by 102CAR-T cell therapy researchImmunotherapy and Immune ResponsesT-cell and B-cell Immunology

Automated manufacture of autologous CD19 CAR-T cells for treatment of non-hodgkin lymphoma

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Jackson, Zachary, Roe, Anne, Sharma, Ashish Arunkumar, Lopes, Filipa Blasco Tavares Pereira, Talla, Aarthi, Kleinsorge-Block, Sarah, Zamborsky, Kayla, Schiavone, Jennifer +16 more·2020·Frontiers in Immunology
DOI 10.3389/fimmu.2020.01941PMC PMC7427107
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Abstract

Chimeric antigen receptor T cells (CAR-T cell) targeting CD19 are effective against several subtypes of CD19-expressing hematologic malignancies. Centralized manufacturing has allowed rapid expansion of this cellular therapy, but it may be associated with treatment delays due to the required logistics. We hypothesized that point of care manufacturing of CAR-T cells on the automated CliniMACS Prodigy® device allows reproducible and fast delivery of cells for the treatment of patients with non-Hodgkin’s lymphoma. Here we describe cell manufacturing results and characterize the phenotype and effector function of CAR-T cells used in a phase I/II study. We utilized a lentiviral vector delivering a second-generation CD19 CAR construct with 4-1BB costimulatory domain and TNFRSF19 transmembrane domain. Our data highlight the successful generation of CAR-T cells at numbers sufficient for all patients treated, a shortened duration of production from twelve to eight days followed by fresh infusion into patients, and the detection of CAR-T cells in patient circulation up to one-year post-infusion.

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  • Fully automated closed processes eliminate any handling of the product during manufacturing but are restricted to a single product in each production run.

    “Fully automated closed processes eliminate any handling of the product during manufacturing but are restricted to a single product in each production run (77-79).”

    From Scalable Manufacturing of CAR T Cells for Cancer Immunotherapy (2021) · cites this paper as [78]

    The Introduction describes CliniMACS Prodigy as a closed automated CAR-T manufacturing system, and the Discussion reports manufacturing with a GMP-compliant closed system. Neither passage says that the product requires no handling during manufacturing or that a production run is restricted to one product; searches for handling and per-run capacity did not establish those claims. Our copy provides no page numbers for these passages. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • In vivo expansion was driven by CD8+ CAR-T cells.

    “The immunophenotypic analysis of these CAR-T cells revealed that the majority of CAR+ cells in their highly active state (within the first month) were CD8+ T cells (CD4/CD8 ratio <0.5), indicating that in vivo expansion was driven by CD8+ CAR-T cells, consistent with a previous report.26”

    From Point-of-care manufacturing of anti-CD19 CAR-T cells using a closed production platform: Experiences of an academic in Thailand (2024) · cites this paper as [26]

  • The LVV was manufactured and tested under a quality management system in compliance with GMP guidelines.

    “The LVV was manufactured and tested under a quality management system in compliance with GMP guidelines and was previously used in numerous clinical studies.26,27,28”

    From Point-of-care manufacturing of anti-CD19 CAR-T cells using a closed production platform: Experiences of an academic in Thailand (2024) · cites this paper as [26]

    The Materials and Methods section (“Lentiviral Vector”; page unavailable) identifies the LVV used and its provider, but does not describe how it was manufactured or tested. The Introduction and Discussion describe GMP compliance for the CAR-T cell manufacturing system, not a quality management system for the LVV. Searches for vector production, quality control, and GMP testing found no passage addressing the claim. (LLM, conf=0.74)

    Experimental — accuracy not yet measured

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References 34 · Cited by 102

Research works printed but not linked: 29

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Authors
Jackson, Z., Roe, A., Sharma, A. A., Lopes, F. B. T. P., Talla, A., Kleinsorge-Block, S., Zamborsky, K., Schiavone, J., Manjappa, S., Schauner, R., Lee, G., Liu, R., Caimi, P. F., Xiong, Y., Krueger, W., Worden, A., Kadan, M., Schneider, D., Orentas, R., Dropulic, B., Sekaly, R.-P., de Lima, M., Wald, D. N., & Reese, J. S.
Affiliations
  • Case Western Reserve University (US)
  • The Alan Turing Institute (GB)
  • University Hospitals Seidman Cancer Center (US)
  • University Hospitals of Cleveland (US)
  • Lentigen Technology (United States) (US)
  • University of Washington (US)
  • University Hospitals Cleveland Medical Center (US)
Corresponding author
  • Wald, David N.
  • Reese, Jane S.
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2020-08-07
Volume
11
Pages
1941-1941
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2020.01941
PMC
PMC7427107
OpenAlex
W3048276742
Cited by
102
References
34
Citations by year
2026: 12 · 2025: 14 · 2024: 18 · 2023: 17 · 2022: 26 · 2021: 13 · 2020: 2
FWCI
5.24
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Cancer Institute
Topics
  • Health Sciences › Medicine › Oncology › CAR-T cell therapy research
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
CD19 CAR T cells, non-Hodgkin lymphoma, point-of-care manufacturing, CliniMACS Prodigy, autologous T cells, lentiviral vectors, 4-1BB costimulation, TNFRSF19, second-generation CAR, CAR T cell persistence, effector function, hematologic malignancies
MeSH terms
Receptors, Chimeric Antigen, Animals, Automation, Cells, Cultured, Cytotoxicity, Immunologic, Humans, Lymphoma, Non-Hodgkin, Phenotype, T-Lymphocytes, Transplantation, Autologous, Immunotherapy, Adoptive, Workload, Mice, Inbred NOD, Treatment Outcome, Clinical Trials, Phase I as Topic, Clinical Trials, Phase II as Topic, Cell Culture Techniques, Antigens, CD19, Point-of-Care Systems, Xenograft Model Antitumor Assays, Cell Engineering

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