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.

免疫检查点阻断 （ICB） 疗法已成为多种晚期癌症的新治疗范式，但低反应率阻碍了广泛的临床应用。在这里，我们使用基于肽的仿生自组装策略来生成纳米颗粒 TPM1，用于在肿瘤细胞表面结合 PD-L1。与 PD-L1 结合后，TPM1 原位转化为纤维状网络，以促进结合和未结合的 PD-L1 的聚集，从而导致 PD-1/PD-L1 通路的阻断。TPM1 的特征表明在肿瘤中的滞留时间延长（> 7 天）和与在多个小鼠肿瘤模型中重新激活 CD8⁺ T 细胞相关的抗癌作用。因此，我们的结果表明 TPM1 是增强 ICB 疗效的潜在策略。