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

• Verfasst von: Gong, Wenjie [VerfasserIn]
• Verfasst von: Hoffmann, Jean-Marc [VerfasserIn]
• Verfasst von: Stock, Sophia [VerfasserIn]
• Verfasst von: Wang, Lei [VerfasserIn]
• Verfasst von: Liu, Yibin [VerfasserIn]
• Verfasst von: Schubert, Maria-Luisa [VerfasserIn]
• Verfasst von: Neuber, Brigitte [VerfasserIn]
• Verfasst von: Hückelhoven-Krauss, Angela [VerfasserIn]
• Verfasst von: Gern, Ulrike [VerfasserIn]
• Verfasst von: Schmitt, Anita [VerfasserIn]
• Verfasst von: Müller-Tidow, Carsten [VerfasserIn]
• Verfasst von: Shiku, Hiroshi [VerfasserIn]
• Verfasst von: Schmitt, Michael [VerfasserIn]
• Verfasst von: Sellner, Leopold [VerfasserIn]
• Titel: Comparison of IL-2 vs IL-7/IL-15 for the generation of NY-ESO-1-specific T cells
• Verf.angabe: 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
• E-Jahr: 2019
• Jahr: 8 June 2019
• Umfang: 15 S.
• Fussnoten: Published online: 8 June 2019 ; Gesehen am 16.10.2019
• Titel Quelle: Enthalten in: Cancer immunology immunotherapy
• Ort Quelle: Berlin : Springer, 1976
• Jahr Quelle: 2019
• Band/Heft Quelle: 68(2019), 7, Seite 1195-1209
• ISSN Quelle: 1432-0851
• DOI: doi:10.1007/s00262-019-02354-4
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Adoptive T cell transfer
• Sach-SW: Interleukin
• Sach-SW: NY-ESO-1
• Sach-SW: T cell receptor
• K10plus-PPN: 1678972096

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 (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.