Cited by 765CAR-T cell therapy researchImmunotherapy and Immune ResponsesVirus-based gene therapy research

Global Manufacturing of CAR T Cell Therapy

Open access
Levine, Bruce L., Miskin, James, Wonnacott, Keith, Keir, Christopher·2017·Molecular Therapy - Methods & Clinical Development

Abstract

Immunotherapy using chimeric antigen receptor-modified T cells has demonstrated high response rates in patients with B cell malignancies, and chimeric antigen receptor T cell therapy is now being investigated in several hematologic and solid tumor types. Chimeric antigen receptor T cells are generated by removing T cells from a patient's blood and engineering the cells to express the chimeric antigen receptor, which reprograms the T cells to target tumor cells. As chimeric antigen receptor T cell therapy moves into later-phase clinical trials and becomes an option for more patients, compliance of the chimeric antigen receptor T cell manufacturing process with global regulatory requirements becomes a topic for extensive discussion. Additionally, the challenges of taking a chimeric antigen receptor T cell manufacturing process from a single institution to a large-scale multi-site manufacturing center must be addressed. We have anticipated such concerns in our experience with the CD19 chimeric antigen receptor T cell therapy CTL019. In this review, we discuss steps involved in the cell processing of the technology, including the use of an optimal vector for consistent cell processing, along with addressing the challenges of expanding chimeric antigen receptor T cell therapy to a global patient population.

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Crossref · 10.1016/j.omtm.2016.12.006

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  • Autologous CAR T cells have sometimes suffered manufacturing delays and, in some instances, had difficulty meeting target doses in commercial production.

    “Despite clinical success, autologous CAR T cells have sometimes suffered manufacturing delays and, in some instances, had difficulty meeting target doses in commercial production (23).”

    From Scalable Manufacturing of CAR T Cells for Cancer Immunotherapy (2021) · cites this paper as [23]

    The sections on scaling manufacturing and ensuring product quality discuss potential challenges, but do not report manufacturing delays or instances in which commercial production failed to meet target CAR T-cell doses. Searches for delays, dose, and target specifications found no passage establishing those events; the target-specifications passage concerns viral vector production instead. (LLM, conf=0.75)

    Experimental — accuracy not yet measured
  • The LVVs have been used to alter T cells by introducing genes to generate immunity to fight cancer through the delivery of chimeric antigen receptors (CARs) or cloned T-cell receptors.

    “The LVVs have been used to alter T cells by introducing genes to generate immunity to fight cancer through the delivery of chimeric antigen receptors (CARs) or cloned T-cell receptors.”

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Research works printed but not linked: 1

  1. [23]Coffin J. Hughes S. Varmus H. Retroviruses 1997 Cold Spring Harbor Laboratory Press Cold Spring Harbor, NY 21433340

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Authors
Levine, B. L., Miskin, J., Wonnacott, K., & Keir, C.
Affiliations
  • University of Pennsylvania (US)
  • Oxford BioMedica (United Kingdom) (GB)
Corresponding author
Levine, Bruce L.
Venue
Molecular Therapy - Methods & Clinical Development
Publisher
Elsevier BV
Published
2017-03
Volume
4
Pages
92-101
ISSN
2329-0501 (ISSN-L)
OpenAlex
W2567664749
Cited by
765
References
61
Citations by year
2026: 80 · 2025: 85 · 2024: 100 · 2023: 98 · 2022: 79 · 2021: 88 · 2020: 83 · 2019: 68 · 2018: 65 · 2017: 15 · 2013: 1
FWCI
6.63
Type
journal article
Language
en
Open access
Locations
  • Molecular Therapy — Methods & Clinical Development (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Novartis Pharmaceuticals
Topics
  • Health Sciences › Medicine › Oncology › CAR-T cell therapy research
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Keywords
CAR T-cell therapy, chimeric antigen receptor, cell manufacturing, regulatory compliance, CD19, tisagenlecleucel, multi-objective optimization, B-cell malignancies, hematologic malignancies, solid tumors, cell processing

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