Immunostimulatory DNA Tetrahedron‐Based Nanovaccine Combined With Immune Checkpoint PD‐1 Blockade for Boosting Systemic Immune Responses Against Oral Squamous Cell Carcinoma
ABSTRACT Despite advancements in immune checkpoint blockade (ICB) therapies for treating various tumors, the immunosuppressive environment in oral squamous cell carcinoma (OSCC) significantly limits therapeutic efficacy. Tumor vaccines, which offer great potential for cancer immunotherapy, still fac...
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2025-07-01
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| Online Access: | https://doi.org/10.1002/agt2.70061 |
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| author | Xueting Yang Yun Wang Yan Yang Sicheng Zhang Dianri Wang Yi Luo Chunyan Shui Yongcong Cai Ruoyi Yang Shuang Dong Mu Yang Yunfeng Lin Chao Li |
| author_facet | Xueting Yang Yun Wang Yan Yang Sicheng Zhang Dianri Wang Yi Luo Chunyan Shui Yongcong Cai Ruoyi Yang Shuang Dong Mu Yang Yunfeng Lin Chao Li |
| author_sort | Xueting Yang |
| collection | DOAJ |
| description | ABSTRACT Despite advancements in immune checkpoint blockade (ICB) therapies for treating various tumors, the immunosuppressive environment in oral squamous cell carcinoma (OSCC) significantly limits therapeutic efficacy. Tumor vaccines, which offer great potential for cancer immunotherapy, still face challenges like potential mutation risks, rapid elimination, and low in vivo delivery efficiency. In this study, we fabricate an immunostimulatory nanovaccine using tetrahedral framework nucleic acids (tFNAs) as a carrier for stable and efficient delivery of CpG oligonucleotide. Then an intensive tumor immunotherapeutic strategy by combining tFNA‐CpG nanovaccine with PD‐1 inhibitor is used in OSCC tumor‐bearing mice. Intravenous administration of the tFNA‐CpG nanovaccine effectively activates the antigen‐presenting cells (APCs), resulting in an increased proportion of M1‐like macrophages and mature dendritic cells, accompanied by heightened production of inflammatory cytokines IL‐1β, IL‐12, and IL‐6. When combined with ICB therapy, the anti‐PD‐1 drug inhibits the PD‐1/PD‐L1 interaction within tumor microenvironment. Subsequently, the APCs activated by tFNA‐CpG facilitate the phenotypic differentiation of T cells, resulting in a substantial boost in infiltration of cytotoxic T cells (expressing IFN‐γ and Granzyme B) in both lymph nodes and tumor tissues, thereby executing a potent antitumor effect and inhibiting the progression of OSCC tumors in C3H mouse. Therefore, this study presents an attractive approach to overcoming current ICB limitations in OSCC immunotherapy and provides new avenues for future clinical practice. |
| format | Article |
| id | doaj-art-c7a6074616144adabe5ad523eb742d5f |
| institution | Kabale University |
| issn | 2692-4560 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
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| spelling | doaj-art-c7a6074616144adabe5ad523eb742d5f2025-08-20T03:28:13ZengWileyAggregate2692-45602025-07-0167n/an/a10.1002/agt2.70061Immunostimulatory DNA Tetrahedron‐Based Nanovaccine Combined With Immune Checkpoint PD‐1 Blockade for Boosting Systemic Immune Responses Against Oral Squamous Cell CarcinomaXueting Yang0Yun Wang1Yan Yang2Sicheng Zhang3Dianri Wang4Yi Luo5Chunyan Shui6Yongcong Cai7Ruoyi Yang8Shuang Dong9Mu Yang10Yunfeng Lin11Chao Li12Department of Head and Neck Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center University of Electronic Science and Technology of China Chengdu P. R. ChinaState Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Sichuan University Chengdu P. R. ChinaDepartment of Head and Neck Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center University of Electronic Science and Technology of China Chengdu P. R. ChinaDepartment of Head and Neck Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center University of Electronic Science and Technology of China Chengdu P. R. ChinaDepartment of Head and Neck Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center University of Electronic Science and Technology of China Chengdu P. R. ChinaDepartment of Head and Neck Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center University of Electronic Science and Technology of China Chengdu P. R. ChinaDepartment of Head and Neck Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center University of Electronic Science and Technology of China Chengdu P. R. ChinaDepartment of Head and Neck Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center University of Electronic Science and Technology of China Chengdu P. R. ChinaDepartment of Head and Neck Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center University of Electronic Science and Technology of China Chengdu P. R. ChinaDepartment of Head and Neck Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center University of Electronic Science and Technology of China Chengdu P. R. ChinaDepartment of Head and Neck Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center University of Electronic Science and Technology of China Chengdu P. R. ChinaState Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Sichuan University Chengdu P. R. ChinaDepartment of Head and Neck Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center University of Electronic Science and Technology of China Chengdu P. R. ChinaABSTRACT Despite advancements in immune checkpoint blockade (ICB) therapies for treating various tumors, the immunosuppressive environment in oral squamous cell carcinoma (OSCC) significantly limits therapeutic efficacy. Tumor vaccines, which offer great potential for cancer immunotherapy, still face challenges like potential mutation risks, rapid elimination, and low in vivo delivery efficiency. In this study, we fabricate an immunostimulatory nanovaccine using tetrahedral framework nucleic acids (tFNAs) as a carrier for stable and efficient delivery of CpG oligonucleotide. Then an intensive tumor immunotherapeutic strategy by combining tFNA‐CpG nanovaccine with PD‐1 inhibitor is used in OSCC tumor‐bearing mice. Intravenous administration of the tFNA‐CpG nanovaccine effectively activates the antigen‐presenting cells (APCs), resulting in an increased proportion of M1‐like macrophages and mature dendritic cells, accompanied by heightened production of inflammatory cytokines IL‐1β, IL‐12, and IL‐6. When combined with ICB therapy, the anti‐PD‐1 drug inhibits the PD‐1/PD‐L1 interaction within tumor microenvironment. Subsequently, the APCs activated by tFNA‐CpG facilitate the phenotypic differentiation of T cells, resulting in a substantial boost in infiltration of cytotoxic T cells (expressing IFN‐γ and Granzyme B) in both lymph nodes and tumor tissues, thereby executing a potent antitumor effect and inhibiting the progression of OSCC tumors in C3H mouse. Therefore, this study presents an attractive approach to overcoming current ICB limitations in OSCC immunotherapy and provides new avenues for future clinical practice.https://doi.org/10.1002/agt2.70061immune checkpoint blockadenanovaccinesoral squamous cell carcinomatetrahedral framework nucleic acidstumor immunotherapy |
| spellingShingle | Xueting Yang Yun Wang Yan Yang Sicheng Zhang Dianri Wang Yi Luo Chunyan Shui Yongcong Cai Ruoyi Yang Shuang Dong Mu Yang Yunfeng Lin Chao Li Immunostimulatory DNA Tetrahedron‐Based Nanovaccine Combined With Immune Checkpoint PD‐1 Blockade for Boosting Systemic Immune Responses Against Oral Squamous Cell Carcinoma Aggregate immune checkpoint blockade nanovaccines oral squamous cell carcinoma tetrahedral framework nucleic acids tumor immunotherapy |
| title | Immunostimulatory DNA Tetrahedron‐Based Nanovaccine Combined With Immune Checkpoint PD‐1 Blockade for Boosting Systemic Immune Responses Against Oral Squamous Cell Carcinoma |
| title_full | Immunostimulatory DNA Tetrahedron‐Based Nanovaccine Combined With Immune Checkpoint PD‐1 Blockade for Boosting Systemic Immune Responses Against Oral Squamous Cell Carcinoma |
| title_fullStr | Immunostimulatory DNA Tetrahedron‐Based Nanovaccine Combined With Immune Checkpoint PD‐1 Blockade for Boosting Systemic Immune Responses Against Oral Squamous Cell Carcinoma |
| title_full_unstemmed | Immunostimulatory DNA Tetrahedron‐Based Nanovaccine Combined With Immune Checkpoint PD‐1 Blockade for Boosting Systemic Immune Responses Against Oral Squamous Cell Carcinoma |
| title_short | Immunostimulatory DNA Tetrahedron‐Based Nanovaccine Combined With Immune Checkpoint PD‐1 Blockade for Boosting Systemic Immune Responses Against Oral Squamous Cell Carcinoma |
| title_sort | immunostimulatory dna tetrahedron based nanovaccine combined with immune checkpoint pd 1 blockade for boosting systemic immune responses against oral squamous cell carcinoma |
| topic | immune checkpoint blockade nanovaccines oral squamous cell carcinoma tetrahedral framework nucleic acids tumor immunotherapy |
| url | https://doi.org/10.1002/agt2.70061 |
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