Skip to content
DraconiticResearch
Search Sources API
210,049 studies31 sourcesUpdated 41 min ago
Peer-reviewedCC BY 4.0Advanced Science

Repurposing a Small Molecule Plant Hormone as a Tunable ON‐Switch for CAR‐T Cell Immunotherapy

  • Hongxiang Zeng1,2
  • Lei Zheng3,4
  • Rongkun Tao5
  • Sirui Zheng1,2
  • Yanke Zhong1,2
  • Yongxia Niu1,2
  • Peng Zhang1,2
  • Xiang Ma1,2
  • Chen Yang1,2
  • Min Zhang1,2
  • Fuyu Duan1,2
  • Jing Yang1,2
5 more authors
  • Xuan Wei1,2
  • Xiang Zhou2
  • Zhenbiao Yang1,2,6
  • Zhaoxi Sun1
  • Qizhou Lian1,2,7,8
8 affiliations
  1. 1Faculty of Synthetic Biology and Institute of Cell and Gene Technology Shenzhen University of Advanced Technology Shenzhen China
  2. 2State Key Laboratory of Quantitative Synthetic Biology Shenzhen Institute of Synthetic Biology Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences Shenzhen China
  3. 3Department of Chemistry New York University New York USA
  4. 4New York University–East China Normal University Center for Computational Chemistry School of Chemistry and Molecular Engineering New York University Shanghai Shanghai China
  5. 5The First Affiliated Hospital of Xiamen University School of Medicine Clinical Research Institute Xiamen University Xiamen China
  6. 6Institute of Emerging Agricultural Technology Shenzhen University of Advanced Technology Shenzhen China
  7. 7Center For Translational Stem Cell Biology Hong Kong and State Key Laboratory of Pharmaceutical Biotechnology The University of Hong Kong Hong Kong SAR China
  8. 8Prenatal Diagnostic Center and Cord Blood Bank Guangzhou Women and Children's Medical Centre Guangzhou Medical University Guangzhou China
Read full textDOICite

Abstract

Precise regulation of chimeric antigen receptor (CAR)‐T cell activity is essential to maximize efficacy and minimize toxicity. While switch‐controlled CAR‐T holds great promise, challenges remain in achieving accurate activation, reducing immunogenicity, and preventing off‐target effects. Here we present a novel inducible ON‐switch CAR design that leverages plant hormone signaling components to achieve controllable T cell activation. By engineering a receptor system integrating the plant auxin receptor AFB1 with its co‐receptor IAA7, we enable ligand‐dependent interactions triggered by the plant hormone auxins. This design allows rapid, reversible, and dose‐dependent T cell activation, resulting in potent cytotoxicity against B‐cell lymphoma in vitro and in vivo. Notably, auxCAR‐T cells controlled by synthetic auxin analogs maintain a favorable memory phenotype and exhibit reduced functional exhaustion during treatment, leading to improved therapeutic efficacy. Our plant hormone‐based orthogonal system overcomes key limitations of existing switch systems and advances the development of precision CAR‐T therapies.

Related

  1. Association of baseline hormone levels with outcomes of first-line immunotherapy in extensive-stage small cell lung cancer
    Shuxing Wang, Rui Meng, Jiheng Liu +17
    Translational Lung Cancer ResearchPeer-reviewedCC BY-NC-NDFull textOncologyEurope PMC
  2. A dual-switch safety system enables safety controllability and high-efficiency enrichment for T cell immunotherapy
    Hongtao Liu, Huimin Wang, Bo Hou +4
    Molecular Therapy AdvancesPeer-reviewedCC BY 4.0Full textOncologyPMC
  3. Drug repurposing: Landmark achievements in translational medicine
    Jacek Z. Kubiak
    Journal of Clinical and Translational ResearchPeer-reviewedCC BY-NCFull textMedical imaging & radiologyHAL
  4. Senescence-Associated Transcriptome Reversal Prioritizes Repurposing Candidates for Diabetic Kidney Disease: A Computational Study
    Duygu Aygüneş-Jafari, Zekeriya Düzgün
    BiomedicinesPeer-reviewedCC BYFull textGeneral medicineEurope PMC
  5. Repurposing, redefining, and reimagining: A paradigm shift towards person-driven neuroscience in the digital age
    Becky Inkster, Mark Sheppard
    PsyArXivPreprintAll rights reservedFull textNeurosciencePsychiatry & mental healthOSF

Cite

BibTeXRIS
BibTeX
@article{zeng2026repurposing,
  title = {{Repurposing a Small Molecule Plant Hormone as a Tunable ON‐Switch for CAR‐T Cell Immunotherapy}},
  author = {Hongxiang Zeng and Lei Zheng and Rongkun Tao and Sirui Zheng and Yanke Zhong and Yongxia Niu and Peng Zhang and Xiang Ma and Chen Yang and Min Zhang and Fuyu Duan and Jing Yang and Xuan Wei and Xiang Zhou and Zhenbiao Yang and Zhaoxi Sun and Qizhou Lian},
  journal = {Advanced Science},
  year = {2026},
  month = aug,
  doi = {10.1002/advs.77020},
  url = {https://doi.org/10.1002/advs.77020},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Repurposing a Small Molecule Plant Hormone as a Tunable ON‐Switch for CAR‐T Cell Immunotherapy
AU  - Hongxiang Zeng
AU  - Lei Zheng
AU  - Rongkun Tao
AU  - Sirui Zheng
AU  - Yanke Zhong
AU  - Yongxia Niu
AU  - Peng Zhang
AU  - Xiang Ma
AU  - Chen Yang
AU  - Min Zhang
AU  - Fuyu Duan
AU  - Jing Yang
AU  - Xuan Wei
AU  - Xiang Zhou
AU  - Zhenbiao Yang
AU  - Zhaoxi Sun
AU  - Qizhou Lian
PY  - 2026
DA  - 2026/08/11
JO  - Advanced Science
DO  - 10.1002/advs.77020
UR  - https://doi.org/10.1002/advs.77020
AB  - Precise regulation of chimeric antigen receptor (CAR)‐T cell activity is essential to maximize efficacy and minimize toxicity. While switch‐controlled CAR‐T holds great promise, challenges remain in achieving accurate activation, reducing immunogenicity, and preventing off‐target effects. Here we present a novel inducible ON‐switch CAR design that leverages plant hormone signaling components to achieve controllable T cell activation. By engineering a receptor system integrating the plant auxin receptor AFB1 with its co‐receptor IAA7, we enable ligand‐dependent interactions triggered by the plant hormone auxins. This design allows rapid, reversible, and dose‐dependent T cell activation, resulting in potent cytotoxicity against B‐cell lymphoma in vitro and in vivo. Notably, auxCAR‐T cells controlled by synthetic auxin analogs maintain a favorable memory phenotype and exhibit reduced functional exhaustion during treatment, leading to improved therapeutic efficacy. Our plant hormone‐based orthogonal system overcomes key limitations of existing switch systems and advances the development of precision CAR‐T therapies.
SN  - 2198-3844
ER  -