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Cited by 73CAR-T cell therapy researchImmunotherapy and Immune ResponsesT-cell and B-cell Immunology

Clinical-scale selection and viral transduction of human naïve and central memory CD8+ T cells for adoptive cell therapy of cancer patients

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Casati, Anna, Varghaei-Nahvi, Azam, Feldman, Steven Alexander, Assenmacher, Mario, Rosenberg, Steven Aaron, Dudley, Mark Edward, Scheffold, Alexander·2013·Cancer Immunology, Immunotherapy
DOI 10.1007/s00262-013-1459-xPMC PMC6348480
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Abstract

The adoptive transfer of lymphocytes genetically engineered to express tumor-specific antigen receptors is a potent strategy to treat cancer patients. T lymphocyte subsets, such as naïve or central memory T cells, selected in vitro prior to genetic engineering have been extensively investigated in preclinical mouse models, where they demonstrated improved therapeutic efficacy. However, so far, this is challenging to realize in the clinical setting, since good manufacturing practices (GMP) procedures for complex cell sorting and genetic manipulation are limited. To be able to directly compare the immunological attributes and therapeutic efficacy of naïve (T(N)) and central memory (T(CM)) CD8(+) T cells, we investigated clinical-scale procedures for their parallel selection and in vitro manipulation. We also evaluated currently available GMP-grade reagents for stimulation of T cell subsets, including a new type of anti-CD3/anti-CD28 nanomatrix. An optimized protocol was established for the isolation of both CD8(+) T(N) cells (CD4(-)CD62L(+)CD45RA(+)) and CD8(+) T(CM) (CD4(-)CD62L(+)CD45RA(-)) from a single patient. The highly enriched T cell subsets can be efficiently transduced and expanded to large cell numbers, sufficient for clinical applications and equivalent to or better than current cell and gene therapy approaches with unselected lymphocyte populations. The GMP protocols for selection of T(N) and T(CM) we reported here will be the basis for clinical trials analyzing safety, in vivo persistence and clinical efficacy in cancer patients and will help to generate a more reliable and efficacious cellular product.

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  • Most clinical protocols and all commercially approved therapies have relied on viral vectors to deliver CAR transgenes into T cells.

    “Further, most clinical protocols, and all the commercially approved therapies, have relied on viral vectors to deliver CAR transgenes into T cells (9-14,24-26).”

    From Scalable Manufacturing of CAR T Cells for Cancer Immunotherapy (2021) · cites this paper as [24]

    The Introduction (page unavailable) describes retroviral transduction as a current standard T-cell protocol, and Materials and methods (page unavailable) reports using a retroviral vector. But the vector in this study delivered a TCR, not a CAR; the paper does not establish that most CAR clinical protocols or all commercially approved CAR therapies used viral vectors. (LLM, conf=0.86)

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Research works printed but not linked: 45

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Authors
Casati, A., Varghaei-Nahvi, A., Feldman, S. A., Assenmacher, M., Rosenberg, S. A., Dudley, M. E., & Scheffold, A.
Affiliations
  • Miltenyi Biotec (Germany) (DE)
  • National Institutes of Health (US)
  • Leibniz Association (DE)
Corresponding author
Scheffold, Alexander
ORCID
Venue
Cancer Immunology, Immunotherapy
Publisher
Springer Science and Business Media LLC
Published
2013-08-01
Volume
62
Issue
10
Pages
1563-1573
ISSN
  • 0340-7004 (ISSN-L)
  • 1432-0851
DOI
10.1007/s00262-013-1459-x
PMC
PMC6348480
OpenAlex
W2021122662
Cited by
73
References
0
Citations by year
2026: 6 · 2025: 5 · 2024: 6 · 2023: 4 · 2022: 9 · 2021: 7 · 2020: 4 · 2019: 4 · 2018: 7 · 2017: 3 · 2016: 9 · 2015: 6 · 2014: 2
FWCI
3.04
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Cancer Immunology Immunotherapy (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Cancer Institute (Z01BC010984)
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
adoptive immunotherapy, naive CD8+ T cells, CD8+ central memory T cells, T cell selection, viral transduction, GMP cell manufacturing, T cell expansion, L-selectin, CD45RA
MeSH terms
Cell Differentiation, Humans, Immunologic Memory, Melanoma, Transduction, Genetic, Immunophenotyping, T-Lymphocyte Subsets, Immunotherapy, Adoptive, CD8-Positive T-Lymphocytes

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