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

Chih-Jia Chao, Endong Zhang, 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, Steve Seung-Young Lee, Yu Gao, Peng Zhang and Zongmin Zhao ()
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Chih-Jia Chao: University of Illinois Chicago
Endong Zhang: University of Illinois Chicago
Duong N. Trinh: University of Illinois Chicago
Edidiong Udofa: University of Illinois Chicago
Hanchen Lin: Northwestern University Feinberg School of Medicine
Caylee Silvers: Northwestern University Feinberg School of Medicine
Jiawei Huo: Northwestern University Feinberg School of Medicine
Shan He: University of Illinois Chicago
Jingtian Zheng: University of Illinois Chicago
Xiaoying Cai: University of Illinois Chicago
Qing Bao: University of Illinois Chicago
Luyu Zhang: University of Illinois Chicago
Philana Phan: University of Illinois Chicago
Sara M. Elgendy: University of Illinois Chicago
Xiangqian Shi: University of Illinois Chicago
Joanna E. Burdette: University of Illinois Chicago
Steve Seung-Young Lee: University of Illinois Chicago
Yu Gao: University of Illinois Chicago
Peng Zhang: Northwestern University Feinberg School of Medicine
Zongmin Zhao: University of Illinois Chicago

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-59840-w

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