Integrating antigen capturing nanoparticles and type 1 conventional dendritic cell therapy for in situ cancer immunization
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 integra...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59840-w |
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| author | 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 Zongmin Zhao |
| author_facet | 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 Zongmin Zhao |
| author_sort | Chih-Jia Chao |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c85d2c5708f04ee597e4d37331d29dea |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-c85d2c5708f04ee597e4d37331d29dea2025-08-20T03:10:31ZengNature PortfolioNature Communications2041-17232025-05-0116112010.1038/s41467-025-59840-wIntegrating antigen capturing nanoparticles and type 1 conventional dendritic cell therapy for in situ cancer immunizationChih-Jia Chao0Endong Zhang1Duong N. Trinh2Edidiong Udofa3Hanchen Lin4Caylee Silvers5Jiawei Huo6Shan He7Jingtian Zheng8Xiaoying Cai9Qing Bao10Luyu Zhang11Philana Phan12Sara M. Elgendy13Xiangqian Shi14Joanna E. Burdette15Steve Seung-Young Lee16Yu Gao17Peng Zhang18Zongmin Zhao19Department of Pharmaceutical Sciences, University of Illinois ChicagoDepartment of Pharmaceutical Sciences, University of Illinois ChicagoDepartment of Pharmaceutical Sciences, University of Illinois ChicagoDepartment of Pharmaceutical Sciences, University of Illinois ChicagoDepartment of Neurological Surgery, Lou and Jean Malnati Brain Tumor Institute, Northwestern University Feinberg School of MedicineDepartment of Neurological Surgery, Lou and Jean Malnati Brain Tumor Institute, Northwestern University Feinberg School of MedicineDepartment of Neurological Surgery, Lou and Jean Malnati Brain Tumor Institute, Northwestern University Feinberg School of MedicineDepartment of Pharmaceutical Sciences, University of Illinois ChicagoDepartment of Pharmaceutical Sciences, University of Illinois ChicagoDepartment of Pharmaceutical Sciences, University of Illinois ChicagoDepartment of Pharmaceutical Sciences, University of Illinois ChicagoDepartment of Pharmaceutical Sciences, University of Illinois ChicagoDepartment of Pharmaceutical Sciences, University of Illinois ChicagoDepartment of Pharmaceutical Sciences, University of Illinois ChicagoDepartment of Pharmaceutical Sciences, University of Illinois ChicagoDepartment of Pharmaceutical Sciences, University of Illinois ChicagoDepartment of Pharmaceutical Sciences, University of Illinois ChicagoDepartment of Pharmaceutical Sciences, University of Illinois ChicagoDepartment of Neurological Surgery, Lou and Jean Malnati Brain Tumor Institute, Northwestern University Feinberg School of MedicineDepartment of Pharmaceutical Sciences, University of Illinois ChicagoAbstract 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.https://doi.org/10.1038/s41467-025-59840-w |
| spellingShingle | 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 Zongmin Zhao Integrating antigen capturing nanoparticles and type 1 conventional dendritic cell therapy for in situ cancer immunization Nature Communications |
| title | Integrating antigen capturing nanoparticles and type 1 conventional dendritic cell therapy for in situ cancer immunization |
| title_full | Integrating antigen capturing nanoparticles and type 1 conventional dendritic cell therapy for in situ cancer immunization |
| title_fullStr | Integrating antigen capturing nanoparticles and type 1 conventional dendritic cell therapy for in situ cancer immunization |
| title_full_unstemmed | Integrating antigen capturing nanoparticles and type 1 conventional dendritic cell therapy for in situ cancer immunization |
| title_short | Integrating antigen capturing nanoparticles and type 1 conventional dendritic cell therapy for in situ cancer immunization |
| title_sort | integrating antigen capturing nanoparticles and type 1 conventional dendritic cell therapy for in situ cancer immunization |
| url | https://doi.org/10.1038/s41467-025-59840-w |
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