Integrating antigen capturing nanoparticles and type 1 conventional dendritic cell therapy for in situ cancer immunization

作者：Chih-Jia Chao, Zhang Endong, Duong N. Trinh, Edidiong Udofa, Hanchen Lin, Caylee Silvers, Jiawei Huo, Shan He, Jingtian Zheng, Xiaoying Cai, Qing Bao, Luyu Zhang, Philana Phan, Sara M. Elgendy, Xiangqian Shi, Joanna E. Burdette, Seung Young Lee, Yu Gao, Peng Zhang, Zongmin Zhao · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-59840-w · 被引用次数：18 · 研究领域：Immunotherapy and Immune Responses、CAR-T cell therapy research、RNA Interference and Gene Delivery

Eliciting a robust immune response against tumors is often hampered by the inadequate presence of effective antigen presenting cells and their suboptimal ability to present antigens within the immunosuppressive tumor microenvironment. Here, we report a cascade antigen relay strategy integrating antigen capturing nanoparticles (AC-NPs) and migratory type 1 conventional dendritic cells (cDC1s), named Antigen Capturing nanoparticle Transformed Dendritic Cell therapy (ACT-DC), to facilitate in situ immunization. AC-NPs are engineered to capture antigens directly from the tumor and facilitate their delivery to adoptively transferred migratory cDC1s, enhancing antigen presentation to the lymph nodes and reshaping the tumor microenvironment. Our findings suggest that ACT-DC improves in situ antigen collection, triggers a robust systemic immune response without the need for exogenous antigens, and transforms the tumor environment into a more "immune-hot" state. In multiple tumor models including colon cancer, melanoma, and glioma, ACT-DC in combination with immune checkpoint inhibitors eliminates primary tumors in 50-100% of treated mice and effectively rejects two separate tumor rechallenges. Collectively, ACT-DC could provide a broadly effective approach for in situ cancer immunization and tumor microenvironment modulation.