Tumor neoantigens as key drivers of significant anti - tumor immunity in triple - negative breast cancer mouse models
Recent studies have highlighted the therapeutic potential of targeting tumor neoantigens in solid tumors; however, its efficacy in breast cancer remains unclear. Here, we evaluate the impact of tumor neoantigen-targeted strategies in a syngeneic mouse mammary carcinoma model. Mice previously exposed...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-09-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558625000855 |
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| author | Yujeong Her Jeong Yeon Kim Hocheol Shin Kwangmin Yu Kyu-Jin Lee Yi Rang Na Sangyong Jon Jung Kyoon Choi Hyeong-Gon Moon |
| author_facet | Yujeong Her Jeong Yeon Kim Hocheol Shin Kwangmin Yu Kyu-Jin Lee Yi Rang Na Sangyong Jon Jung Kyoon Choi Hyeong-Gon Moon |
| author_sort | Yujeong Her |
| collection | DOAJ |
| description | Recent studies have highlighted the therapeutic potential of targeting tumor neoantigens in solid tumors; however, its efficacy in breast cancer remains unclear. Here, we evaluate the impact of tumor neoantigen-targeted strategies in a syngeneic mouse mammary carcinoma model. Mice previously exposed to 4T1 tumor cells (PETCs) or treated with tumor cell-derived lysates (TdLs) exhibited robust antitumor immunity, leading to reduced tumor growth and metastasis through tumor immune microenvironment remodeling. TdL administration in mice harboring orthotopic tumors significantly enhanced the efficacy of immune checkpoint blockade, suggesting its potential as an immunotherapeutic adjuvant. To further optimize neoantigen-based approaches, we developed a lipid nanoparticle (LNP)-based delivery system for neoantigen peptides, which effectively suppressed tumor progression and metastasis in vivo. Mechanistically, this strategy promoted antigen-specific T cell activation and reshaped the tumor immune landscape, enhancing immune-mediated tumor rejection. These findings underscore the therapeutic promise of personalized tumor neoantigen-targeted immunotherapy in breast cancer and support its further evaluation in clinical settings. |
| format | Article |
| id | doaj-art-8f22bbf81d4542bc85a8b74833b3bcf5 |
| institution | DOAJ |
| issn | 1476-5586 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj-art-8f22bbf81d4542bc85a8b74833b3bcf52025-08-20T03:09:14ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862025-09-016710120510.1016/j.neo.2025.101205Tumor neoantigens as key drivers of significant anti - tumor immunity in triple - negative breast cancer mouse modelsYujeong Her0Jeong Yeon Kim1Hocheol Shin2Kwangmin Yu3Kyu-Jin Lee4Yi Rang Na5Sangyong Jon6Jung Kyoon Choi7Hyeong-Gon Moon8Interdisciplinary Program in Cancer Biology, Seoul National University College of Medicine, Seoul, Republic of KoreaDepartment of Bio and Brain Engineering, KAIST, Daejeon, Republic of Korea; Penta Medix Co., Ltd., Seongnam, Republic of KoreaDepartment of Biological Sciences, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea; Center for Precision Bio-Nanomedicine, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of KoreaImmunology Core Facility, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of KoreaInterdisciplinary Program in Cancer Biology, Seoul National University College of Medicine, Seoul, Republic of KoreaImmunology Core Facility, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Translational Immunology Lab, Department of Transdisciplinary Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaDepartment of Biological Sciences, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea; Center for Precision Bio-Nanomedicine, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea; Correspondence authors.Department of Bio and Brain Engineering, KAIST, Daejeon, Republic of Korea; Penta Medix Co., Ltd., Seongnam, Republic of Korea; Correspondence authors.Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea; Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea; Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University, Seoul, Republic of Korea; Correspondence authors.Recent studies have highlighted the therapeutic potential of targeting tumor neoantigens in solid tumors; however, its efficacy in breast cancer remains unclear. Here, we evaluate the impact of tumor neoantigen-targeted strategies in a syngeneic mouse mammary carcinoma model. Mice previously exposed to 4T1 tumor cells (PETCs) or treated with tumor cell-derived lysates (TdLs) exhibited robust antitumor immunity, leading to reduced tumor growth and metastasis through tumor immune microenvironment remodeling. TdL administration in mice harboring orthotopic tumors significantly enhanced the efficacy of immune checkpoint blockade, suggesting its potential as an immunotherapeutic adjuvant. To further optimize neoantigen-based approaches, we developed a lipid nanoparticle (LNP)-based delivery system for neoantigen peptides, which effectively suppressed tumor progression and metastasis in vivo. Mechanistically, this strategy promoted antigen-specific T cell activation and reshaped the tumor immune landscape, enhancing immune-mediated tumor rejection. These findings underscore the therapeutic promise of personalized tumor neoantigen-targeted immunotherapy in breast cancer and support its further evaluation in clinical settings.http://www.sciencedirect.com/science/article/pii/S1476558625000855NeoantigenImmunotherapyTriple negative Breast cancerTumor immune microenvironmentCheckpoint blockadeLipid nanoparticle |
| spellingShingle | Yujeong Her Jeong Yeon Kim Hocheol Shin Kwangmin Yu Kyu-Jin Lee Yi Rang Na Sangyong Jon Jung Kyoon Choi Hyeong-Gon Moon Tumor neoantigens as key drivers of significant anti - tumor immunity in triple - negative breast cancer mouse models Neoplasia: An International Journal for Oncology Research Neoantigen Immunotherapy Triple negative Breast cancer Tumor immune microenvironment Checkpoint blockade Lipid nanoparticle |
| title | Tumor neoantigens as key drivers of significant anti - tumor immunity in triple - negative breast cancer mouse models |
| title_full | Tumor neoantigens as key drivers of significant anti - tumor immunity in triple - negative breast cancer mouse models |
| title_fullStr | Tumor neoantigens as key drivers of significant anti - tumor immunity in triple - negative breast cancer mouse models |
| title_full_unstemmed | Tumor neoantigens as key drivers of significant anti - tumor immunity in triple - negative breast cancer mouse models |
| title_short | Tumor neoantigens as key drivers of significant anti - tumor immunity in triple - negative breast cancer mouse models |
| title_sort | tumor neoantigens as key drivers of significant anti tumor immunity in triple negative breast cancer mouse models |
| topic | Neoantigen Immunotherapy Triple negative Breast cancer Tumor immune microenvironment Checkpoint blockade Lipid nanoparticle |
| url | http://www.sciencedirect.com/science/article/pii/S1476558625000855 |
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