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In situ editing of tumour cell membranes induces aggregation and capture of PD-L1 membrane proteins for enhanced cancer immunotherapy

Author

Listed:
  • Chunping Mao

    (Sun Yat-Sen University
    Southern University of Science and Technology
    Southern Medical University
    Sun Yat-Sen University)

  • Fuan Deng

    (Southern University of Science and Technology)

  • Wanning Zhu

    (Sun Yat-Sen University
    Sun Yat-Sen University)

  • Leiming Xie

    (Southern University of Science and Technology)

  • Yijun Wang

    (Southern University of Science and Technology)

  • Guoyin Li

    (Zhoukou Normal University)

  • Xingke Huang

    (Sun Yat-Sen University
    Sun Yat-Sen University)

  • Jiahui Wang

    (Southern University of Science and Technology)

  • Yue Song

    (Southern University of Science and Technology)

  • Ping Zeng

    (Southern University of Science and Technology)

  • Zhenpeng He

    (Southern University of Science and Technology)

  • Jingnan Guo

    (Southern University of Science and Technology)

  • Yao Suo

    (Southern University of Science and Technology)

  • Yujing Liu

    (Southern University of Science and Technology)

  • Zhuo Chen

    (Southern University of Science and Technology)

  • Mingxi Yao

    (Southern University of Science and Technology)

  • Lu Zhang

    (Southern University of Science and Technology)

  • Jun Shen

    (Sun Yat-Sen University
    Sun Yat-Sen University
    Sun Yat-Sen University)

Abstract

Immune checkpoint blockade (ICB) therapy has emerged as a new therapeutic paradigm for a variety of advanced cancers, but wide clinical application is hindered by low response rate. Here we use a peptide-based, biomimetic, self-assembly strategy to generate a nanoparticle, TPM1, for binding PD-L1 on tumour cell surface. Upon binding with PD-L1, TPM1 transforms into fibrillar networks in situ to facilitate the aggregation of both bound and unbound PD-L1, thereby resulting in the blockade of the PD-1/PD-L1 pathway. Characterizations of TPM1 manifest a prolonged retention in tumour ( > 7 days) and anti-cancer effects associated with reinvigorating CD8+ T cells in multiple mice tumour models. Our results thus hint TPM1 as a potential strategy for enhancing the ICB efficacy.

Suggested Citation

  • Chunping Mao & Fuan Deng & Wanning Zhu & Leiming Xie & Yijun Wang & Guoyin Li & Xingke Huang & Jiahui Wang & Yue Song & Ping Zeng & Zhenpeng He & Jingnan Guo & Yao Suo & Yujing Liu & Zhuo Chen & Mingx, 2024. "In situ editing of tumour cell membranes induces aggregation and capture of PD-L1 membrane proteins for enhanced cancer immunotherapy," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54081-9
    DOI: 10.1038/s41467-024-54081-9
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    References listed on IDEAS

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