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Enhanced CAR-T activity against established tumors by polarizing human T cells to secrete interleukin-9

Author

Listed:
  • Lintao Liu

    (Houston Methodist)

  • Enguang Bi

    (Houston Methodist)

  • Xingzhe Ma

    (Houston Methodist)

  • Wei Xiong

    (Houston Methodist)

  • Jianfei Qian

    (Houston Methodist)

  • Lingqun Ye

    (Houston Methodist)

  • Pan Su

    (Houston Methodist)

  • Qiang Wang

    (Houston Methodist)

  • Liuling Xiao

    (Houston Methodist)

  • Maojie Yang

    (Houston Methodist)

  • Yong Lu

    (Wake Forest School of Medicine)

  • Qing Yi

    (Houston Methodist)

Abstract

CAR-T cell therapy is effective for hematologic malignancies. However, considerable numbers of patients relapse after the treatment, partially due to poor expansion and limited persistence of CAR-T cells in vivo. Here, we demonstrate that human CAR-T cells polarized and expanded under a Th9-culture condition (T9 CAR-T) have an enhanced antitumor activity against established tumors. Compared to IL2-polarized (T1) cells, T9 CAR-T cells secrete IL9 but little IFN-γ, express central memory phenotype and lower levels of exhaustion markers, and display robust proliferative capacity. Consequently, T9 CAR-T cells mediate a greater antitumor activity than T1 CAR-T cells against established hematologic and solid tumors in vivo. After transfer, T9 CAR-T cells migrate effectively to tumors, differentiate to IFN-γ and granzyme-B secreting effector memory T cells but remain as long-lived and hyperproliferative T cells. Our findings are important for the improvement of CAR-T cell-based immunotherapy for human cancers.

Suggested Citation

  • Lintao Liu & Enguang Bi & Xingzhe Ma & Wei Xiong & Jianfei Qian & Lingqun Ye & Pan Su & Qiang Wang & Liuling Xiao & Maojie Yang & Yong Lu & Qing Yi, 2020. "Enhanced CAR-T activity against established tumors by polarizing human T cells to secrete interleukin-9," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19672-2
    DOI: 10.1038/s41467-020-19672-2
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    Cited by:

    1. Nicole L. Bertschi & Oliver Steck & Fabian Luther & Cecilia Bazzini & Leonhard Meyenn & Stefanie Schärli & Angela Vallone & Andrea Felser & Irene Keller & Olivier Friedli & Stefan Freigang & Nadja Beg, 2023. "PPAR-γ regulates the effector function of human T helper 9 cells by promoting glycolysis," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Yongyao Fu & Abigail Pajulas & Jocelyn Wang & Baohua Zhou & Anthony Cannon & Cherry Cheuk Lam Cheung & Jilu Zhang & Huaxin Zhou & Amanda Jo Fisher & David T. Omstead & Sabrina Khan & Lei Han & Jean-Ch, 2022. "Mouse pulmonary interstitial macrophages mediate the pro-tumorigenic effects of IL-9," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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