Generation of dual-attribute iTNK cells from hPSCs for cancer immunotherapy

  • Cell Rep Methods. 2024 Sep 16;4(9):100843. doi: 10.1016/j.crmeth.2024.100843.
Yingfeng Zhang  1 ,  Yuanyuan He  1 ,  Chenyi Dai  2 ,  Zhengyang Zhou  1 ,  Yudi Miao  1 ,  Zixin Zhao  1 ,  Qi Lei  3 ,  Cheng Li  4 ,  Chengyan Wang  5 ,  Hongkui Deng  6
Affiliations
  • 1. Peking-Tsinghua Center for Life Sciences, The MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
  • 2. Changping Laboratory, Beijing 102206, China.
  • 3. Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, Peking University Health Science Center, Beijing 100191, China.
  • 4. School of Life Sciences, Center for Bioinformatics, Center for Statistical Science, Peking University, Beijing 100871, China.
  • 5. Peking-Tsinghua Center for Life Sciences, The MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China. Electronic address: [email protected].
  • 6. Peking-Tsinghua Center for Life Sciences, The MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; Changping Laboratory, Beijing 102206, China. Electronic address: [email protected].
PMID: 39216483 DOI: 10.1016/j.crmeth.2024.100843
Abstract

Dual-attribute immune cells possess advantageous features of cytotoxic T cells and natural killer (NK) cells and hold promise for advancing immunotherapy. Dual-attribute cell types such as invariant natural killer T cells, induced T-to-NK cells, and cytokine-induced killer cells have demonstrated efficacy and safety in preclinical and clinical studies. However, their limited availability hinders their widespread application. Human pluripotent stem cells (hPSCs) offer an ideal source. Here, we generate dual-attribute induced T-NK (iTNK) cells from hPSCs, expressing markers of both cytotoxic T and NK cells. Single-cell RNA and T cell receptor (TCR) Sequencing analyses reveal that iTNK cells expressed signature genes associated with both NK and T cells and displayed a diverse TCR repertoire. iTNK cells release cytotoxic mediators, exert cytotoxicity against diverse tumor cell lines, and inhibit tumor growth in vivo. By harnessing adaptive and innate immune responses, hPSC-derived iTNK cells offer promising strategies for Cancer Immunotherapy.

Keywords
CP: Stem cell; NK cell; cytotoxic T cell; hPSCs; iTNK cell; immunotherapy; tumor.
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