2. Academic Validation
  3. A Dendritic Cell-Nanogel Conjugate for Tumor-Draining Lymph Node-Specific PD-L1 Blockade

A Dendritic Cell-Nanogel Conjugate for Tumor-Draining Lymph Node-Specific PD-L1 Blockade

  • Adv Mater. 2025 Jul 7:e2504733. doi: 10.1002/adma.202504733.
Wenzhe Yi 1 2,  Xindi Qian 1,  Dan Yan 1,  Wenlu Yan 1 2,  Shuangshuang Hu 1 3,  Yaping Li 1 2 4,  Dangge Wang 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • 2 University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 3 School of Life Sciences, Jilin University, Changchun, 130012, China.
  • 4 Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, 264000, China.
  • 5 Precision Research Center for Refractory Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
PMID: 40619999 DOI: 10.1002/adma.202504733
Abstract

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.

Keywords

anti‐PD‐L1 antibody; dendritic cells; immunotherapy; tumor‐derived lymph nodes.

Figures
Products