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

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, Mingxi Yao, Lu Zhang () and Jun Shen ()
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Chunping Mao: Sun Yat-Sen University
Fuan Deng: Southern University of Science and Technology
Wanning Zhu: 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
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

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-54081-9

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