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Review
. 2022 Jun 29:10:886637.
doi: 10.3389/fbioe.2022.886637. eCollection 2022.

Influence of Culture Conditions on Ex Vivo Expansion of T Lymphocytes and Their Function for Therapy: Current Insights and Open Questions

Affiliations
Review

Influence of Culture Conditions on Ex Vivo Expansion of T Lymphocytes and Their Function for Therapy: Current Insights and Open Questions

Harish Sudarsanam et al. Front Bioeng Biotechnol. .

Abstract

Ex vivo expansion of T lymphocytes is a central process in the generation of cellular therapies targeted at tumors and other disease-relevant structures, which currently cannot be reached by established pharmaceuticals. The influence of culture conditions on T cell functions is, however, incompletely understood. In clinical applications of ex vivo expanded T cells, so far, a relatively classical standard cell culture methodology has been established. The expanded cells have been characterized in both preclinical models and clinical studies mainly using a therapeutic endpoint, for example antitumor response and cytotoxic function against cellular targets, whereas the influence of manipulations of T cells ex vivo including transduction and culture expansion has been studied to a much lesser detail, or in many contexts remains unknown. This includes the circulation behavior of expanded T cells after intravenous application, their intracellular metabolism and signal transduction, and their cytoskeletal (re)organization or their adhesion, migration, and subsequent intra-tissue differentiation. This review aims to provide an overview of established T cell expansion methodologies and address unanswered questions relating in vivo interaction of ex vivo expanded T cells for cellular therapy.

Keywords: CAR T cell; T lymphocyte (T-cell); cell culture conditions; ex vivo expansion; homing.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Open questions in T cell expansion research. Transduction and culture expansion may influence various aspects in the functionality of therapeutic T cells, which may in turn influence beneficial and adverse effects, as addressed in this review.
FIGURE 2
FIGURE 2
Currently used media formulations for ex vivo expansion of CAR T cells.

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References

    1. Abou-El-Enein M., Elsallab M., Feldman S. A., Fesnak A. D., Heslop H. E., Marks P., et al. (2021). Scalable Manufacturing of CAR T Cells for Cancer Immunotherapy. Blood Cancer Discov. 2 (5), 408–422. 10.1158/2643-3230.bcd-21-0084 - DOI - PMC - PubMed
    1. Abramowski-Mock U., Delhove J. M., Qasim W. (2017). Gene Modified T Cell Therapies for Hematological Malignancies. Hematology/Oncology Clin. N. Am. 31 (5), 913–926. 10.1016/j.hoc.2017.06.005 - DOI - PubMed
    1. Abramson J. S., Palomba M. L., Gordon L. I., Lunning M. A., Wang M., Arnason J., et al. (2020). Lisocabtagene Maraleucel for Patients with Relapsed or Refractory Large B-Cell Lymphomas (TRANSCEND NHL 001): a Multicentre Seamless Design Study. Lancet 396 (10254), 839–852. 10.1016/s0140-6736(20)31366-0 - DOI - PubMed
    1. Aghajanian H., Rurik J. G., Epstein J. A. (2022). CAR-based Therapies: Opportunities for Immuno-Medicine beyond Cancer. Nat. Metab. 4 (2), 163–169. 10.1038/s42255-022-00537-5 - DOI - PMC - PubMed
    1. Albert S., Arndt C., Feldmann A., Bergmann R., Bachmann D., Koristka S., et al. (2017). A Novel Nanobody-Based Target Module for Retargeting of T Lymphocytes to EGFR-Expressing Cancer Cells via the Modular UniCAR Platform. Oncoimmunology 6 (4), e1287246. 10.1080/2162402x.2017.1287246 - DOI - PMC - PubMed

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