Human induced-T-to-natural killer cells have potent anti-tumour activities

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  • dc.contributor.author Jiang, Zhiwu
  • dc.contributor.author Hong, Qilan
  • dc.contributor.author Graf, T. (Thomas)
  • dc.contributor.author Li, Peng
  • dc.date.accessioned 2022-04-25T12:28:19Z
  • dc.date.available 2022-04-25T12:28:19Z
  • dc.date.issued 2022
  • dc.description.abstract Background: Adoptive cell therapy (ACT) is a particularly promising area of cancer immunotherapy, engineered T and NK cells that express chimeric antigen receptors (CAR) are being explored for treating hematopoietic malignancies but exhibit limited clinical benefits for solid tumour patients, successful cellular immunotherapy of solid tumors demands new strategies. Methods: Inactivation of BCL11B were performed by CRISPR/Cas9 in human T cells. Immunophenotypic and transcriptional profiles of sgBCL11B T cells were characterized by cytometer and transcriptomics, respectively. sgBCL11B T cells are further engineered with chimeric antigen receptor. Anti-tumor activity of ITNK or CAR-ITNK cells were evaluated in preclinical and clinical studies. Results: We report that inactivation of BCL11B in human CD8+ and CD4+ T cells induced their reprogramming into induced T-to-natural killer cells (ITNKs). ITNKs contained a diverse TCR repertoire; downregulated T cell-associated genes such as TCF7 and LEF1; and expressed high levels of NK cell lineage-associated genes. ITNKs and chimeric antigen receptor (CAR)-transduced ITNKs selectively lysed a variety of cancer cells in culture and suppressed the growth of solid tumors in xenograft models. In a preliminary clinical study, autologous administration of ITNKs in patients with advanced solid tumors was well tolerated, and tumor stabilization was seen in six out nine patients, with one partial remission. Conclusions: The novel ITNKs thus may be a promising novel cell source for cancer immunotherapy.
  • dc.description.sponsorship This study was supported by the National Key Research and Development Plan (Nos. 2021YFE0202800 to P. L, 2017YFE0131600 to Y. L., and 2019YFA0111500 to X. L.), the National Natural Science Foundation of China (Nos. 81961128003 to P.L., 81972672 to P.L., 81773301 to Z. J., 81870121 to P. L., 81873847 to J. Y, 81872069 to Z. Z, and 32170946 to Z. J.), The Youth Innovation Promotion Association of the Chinese Academy of Sciences (No. 2020351 to Z. J.), the Guangdong Provincial Significant New Drugs Development (Nos. 2019B020202003 to P. L., 2019A1515010062 to Y. Y., and 2020A1515011516 to X. W.), the Guangzhou Science and Technology Plan Project (No. 201907010042 to P. L.), 2020B1212060052, the Frontier Research Program of the Guangzhou Regenerative Medicine and Health Guangdong Laboratory (No. 2018GZR110105003 to P. L.), Science and Technology Planning Project of Guangdong Province,China (2020B1212060052), the Science and Technology Program of Guangzhou, China (No. 202002020083 to X. L.), the Open project of the State Key Laboratory of Respiratory Disease (No. SKLRD-OP-202002 to Z. Z.), and the University Grants Committee/Research Grants Council of the Hong Kong (Project No. AoE/M-401/20), and Innovation and Technology Fund (ITF) from Hong Kong SAR Government
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Jiang Z, Qin L, Tang Y, Liao R, Shi J, He B et al. Human induced-T-to-natural killer cells have potent anti-tumour activities. Biomark Res. 2022 Mar 24;10(1):13. DOI: 10.1186/s40364-022-00358-4
  • dc.identifier.doi http://dx.doi.org/10.1186/s40364-022-00358-4
  • dc.identifier.issn 2050-7771
  • dc.identifier.uri http://hdl.handle.net/10230/52886
  • dc.language.iso eng
  • dc.publisher BioMed Central
  • dc.rights © Zhiwu Jiang et al. 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri https://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Càncer -- Immunoteràpia
  • dc.subject.other Tumors -- Immunoteràpia
  • dc.subject.other Genètica
  • dc.title Human induced-T-to-natural killer cells have potent anti-tumour activities
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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