In situ editing of tumour cell membranes induces aggregation and capture of PD-L1 membrane proteins for enhanced cancer immunotherapy
Chunping Mao, Fu‐An 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, Jun Shen
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. Immune checkpoint blockade therapy such as anti-PD-L1 is efficient for treating specific cancer types, but poor response rates remain a caveat. Here the authors generate a peptide-based, self-assembly nanomaterial that binds and aggregates PD-L1 as a fibrillar networks to enhance the anti-tumour efficacy of anti-PD-L1 in multiple mouse tumour models.