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

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 (TN) phenotypes with greater expansion and long-term persistence. To increase these subsets, we compared the generation of New York esophageal squamous cel...

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Main Authors: Gong, Wenjie (Author) , Hoffmann, Jean-Marc (Author) , Stock, Sophia (Author) , Wang, Lei (Author) , Liu, Yibin (Author) , Schubert, Maria-Luisa (Author) , Neuber, Brigitte (Author) , Hückelhoven-Krauss, Angela (Author) , Gern, Ulrike (Author) , Schmitt, Anita (Author) , Müller-Tidow, Carsten (Author) , Shiku, Hiroshi (Author) , Schmitt, Michael (Author) , Sellner, Leopold (Author)
Format: Article (Journal)
Language:English
Published: 8 June 2019
In: Cancer immunology immunotherapy
Year: 2019, Volume: 68, Issue: 7, Pages: 1195-1209
ISSN:1432-0851
DOI:10.1007/s00262-019-02354-4
Online Access:Verlag, Volltext: https://doi.org/10.1007/s00262-019-02354-4
Verlag: https://doi.org/10.1007/s00262-019-02354-4
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Author Notes: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
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Summary: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 (TN) 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 TN 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 TN. However, the absolute number of TN 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.
Item Description:Published online: 8 June 2019
Gesehen am 16.10.2019
Physical Description:Online Resource
ISSN:1432-0851
DOI:10.1007/s00262-019-02354-4

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