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08.06.2019 | Original Article

Comparison of IL-2 vs IL-7/IL-15 for the generation of NY-ESO-1-specific T cells

verfasst von: Wenjie Gong, Jean-Marc Hoffmann, Sophia Stock, Lei Wang, Yibin Liu, Maria-Luisa Schubert, Brigitte Neuber, Angela Hückelhoven-Krauss, Ulrike Gern, Anita Schmitt, Carsten Müller-Tidow, Hiroshi Shiku, Michael Schmitt, Leopold Sellner

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 7/2019

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Abstract

The anti-tumor efficacy of TCR-engineered T cells in vivo depends largely on less-differentiated subsets such as T cells with naïve-like T cell (T_N) phenotypes with greater expansion and long-term persistence. To increase these subsets, we compared the generation of New York esophageal squamous cell carcinoma-1 (NY-ESO-1)-specific T cells under supplementation with either IL-2 or IL-7/IL-15. PBMCs were transduced with MS3II-NY-ESO-1-siTCR retroviral vector. T cell generation was adapted from a CD19-specific CART cell production protocol. Comparable results in viability, expansion and transduction efficiency of T cells under stimulation with either IL-2 or IL-7/IL-15 were observed. IL-7/IL-15 led to an increase of CD4⁺ T cells and a decrease of CD8⁺ T cells, enriched the amount of T_N among CD4⁺ T cells but not among CD8⁺ T cells. In a ⁵¹Cr release assay, similar specific lysis of NY-ESO-1-positive SW982 sarcoma cells was achieved. However, intracellular cytokine staining revealed a significantly increased production of IFN-γ and TNF-α in T cells generated by IL-2 stimulation. To validate these unexpected findings, NY-ESO-1-specific T cell production was evaluated in another protocol originally established for TCR-engineered T cells. IL-7/IL-15 increased the proportion of T_N. However, the absolute number of T_N did not increase due to a significantly slower expansion of T cells with IL-7/IL-15. In conclusion, IL-7/IL-15 does not seem to be superior to IL-2 for the generation of NY-ESO-1-specific T cells. This is in sharp contrast to the observations in CD19-specific CART cells. Changes of cytokine cocktails should be carefully evaluated for individual vector systems.

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Titel: Comparison of IL-2 vs IL-7/IL-15 for the generation of NY-ESO-1-specific T cells
verfasst von: Wenjie Gong
Jean-Marc Hoffmann
Sophia Stock
Lei Wang
Yibin Liu
Maria-Luisa Schubert
Brigitte Neuber
Angela Hückelhoven-Krauss
Ulrike Gern
Anita Schmitt
Carsten Müller-Tidow
Hiroshi Shiku
Michael Schmitt
Leopold Sellner
Publikationsdatum: 08.06.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 7/2019
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-019-02354-4

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Comparison of IL-2 vs IL-7/IL-15 for the generation of NY-ESO-1-specific T cells

Abstract

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ICI-Therapie in der Schwangerschaft wird gut toleriert

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

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