一种用于肿瘤引流淋巴结特异性 PD-L1 阻断的树突状细胞-纳米凝胶偶联物

Targeted blockade of immune checkpoints within tumor-draining lymph nodes (TDLNs) represents a promising strategy to potentiate immune checkpoint blockade (ICB) therapy.

However, the limited delivery of checkpoint inhibitors to TDLNs and inadequate T cell priming persist as major challenges. In this study, an innovative dendritic cell (DC)-based strategy is developed for the targeted delivery of ICB antibodies to TDLNs. The platform is fabricated by conjugating anti-PD-L1 antibody nanogels with DCs, which are further enhanced by pre-treating DCs with tumor antigens.

Subcutaneous administration enabled DCs to execute their intrinsic TDLN-tropic migration, thus facilitating antibody delivery and release under reductive conditions. The antigen-loaded DCs mobilized T cell immunity, while the anti-PD-L1 antibodies block PD-L1 on dendritic cells and myeloid cells within TDLNs, thereby augmenting systemic antitumor immunity. This approach significantly suppresses breast cancer growth, leading to 83. 3% of treated mice being tumor-free.

This study presents a novel strategy for TDLN-targeted PD-L1 blockade by harnessing the intrinsic TDLN tropism of DCs, unveiling new translational opportunities of combining DC-based vaccination with ICB therapy.