Peptide vaccine-conjugated mesoporous carriers synergize with immunogenic cell death and PD-L1 blockade for amplified immunotherapy of metastatic spinal
Abstract The clinical treatment of metastatic spinal tumor remains a huge challenge owing to the intrinsic limitations of the existing methods. Programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PD-L1) pathway blockade has been explored as a promising immunotherapeutic strategy; h...
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| Format: | Article |
| Language: | English |
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BMC
2021-08-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-021-00975-5 |
| _version_ | 1828359791546728448 |
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| author | Zhenqing Wang Liang Chen Yiqun Ma Xilei Li Annan Hu Huiren Wang Wenxing Wang Xiaomin Li Bo Tian Jian Dong |
| author_facet | Zhenqing Wang Liang Chen Yiqun Ma Xilei Li Annan Hu Huiren Wang Wenxing Wang Xiaomin Li Bo Tian Jian Dong |
| author_sort | Zhenqing Wang |
| collection | DOAJ |
| description | Abstract The clinical treatment of metastatic spinal tumor remains a huge challenge owing to the intrinsic limitations of the existing methods. Programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PD-L1) pathway blockade has been explored as a promising immunotherapeutic strategy; however, their inhibition has a low response rate, leading to the minimal cytotoxic T cell infiltration. To ameliorate the immunosuppressive microenvironment of intractable tumor and further boost the efficacy of immunotherapy, we report an all-round mesoporous nanocarrier composed of an upconverting nanoparticle core and a large-pore mesoporous silica shell (UCMS) that is simultaneously loaded with photosensitizer molecules, the IDO-derived peptide vaccine AL-9, and PD-L1 inhibitor. The IDO-derived peptide can be recognized by the dendritic cells and presented to CD8+ cytotoxic T cells, thereby enhancing the immune response and promoting the killing of the IDO-expressed tumor cells. Meanwhile, the near-infrared (NIR) activated photodynamic therapy (PDT) could induce immunogenic cell death (ICD), which promotes the effector T-cell infiltration. By combining the PDT-elicited ICD, peptide vaccine and immune checkpoint blockade, the designed UCMS@Pep-aPDL1 successfully potentiated local and systemic antitumor immunity and reduced the progression of metastatic foci, demonstrating a synergistic strategy for cancer immunotherapy. |
| first_indexed | 2024-04-14T03:45:54Z |
| format | Article |
| id | doaj.art-37a2e4ebec8841849ae95e41e1370fcc |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-14T03:45:54Z |
| publishDate | 2021-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-37a2e4ebec8841849ae95e41e1370fcc2022-12-22T02:14:14ZengBMCJournal of Nanobiotechnology1477-31552021-08-0119111610.1186/s12951-021-00975-5Peptide vaccine-conjugated mesoporous carriers synergize with immunogenic cell death and PD-L1 blockade for amplified immunotherapy of metastatic spinalZhenqing Wang0Liang Chen1Yiqun Ma2Xilei Li3Annan Hu4Huiren Wang5Wenxing Wang6Xiaomin Li7Bo Tian8Jian Dong9Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan UniversityMaterdicine Lab, School of Life Sciences, Shanghai UniversityDepartment of Orthopaedic Surgery, Zhongshan Hospital, Fudan UniversityDepartment of Orthopaedic Surgery, Zhongshan Hospital, Fudan UniversityDepartment of Orthopaedic Surgery, Zhongshan Hospital, Fudan UniversityDepartment of Orthopaedic Surgery, Zhongshan Hospital, Fudan UniversityMaterdicine Lab, School of Life Sciences, Shanghai UniversityMaterdicine Lab, School of Life Sciences, Shanghai UniversityDepartment of Orthopaedic Surgery, Zhongshan Hospital, Fudan UniversityDepartment of Orthopaedic Surgery, Zhongshan Hospital, Fudan UniversityAbstract The clinical treatment of metastatic spinal tumor remains a huge challenge owing to the intrinsic limitations of the existing methods. Programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PD-L1) pathway blockade has been explored as a promising immunotherapeutic strategy; however, their inhibition has a low response rate, leading to the minimal cytotoxic T cell infiltration. To ameliorate the immunosuppressive microenvironment of intractable tumor and further boost the efficacy of immunotherapy, we report an all-round mesoporous nanocarrier composed of an upconverting nanoparticle core and a large-pore mesoporous silica shell (UCMS) that is simultaneously loaded with photosensitizer molecules, the IDO-derived peptide vaccine AL-9, and PD-L1 inhibitor. The IDO-derived peptide can be recognized by the dendritic cells and presented to CD8+ cytotoxic T cells, thereby enhancing the immune response and promoting the killing of the IDO-expressed tumor cells. Meanwhile, the near-infrared (NIR) activated photodynamic therapy (PDT) could induce immunogenic cell death (ICD), which promotes the effector T-cell infiltration. By combining the PDT-elicited ICD, peptide vaccine and immune checkpoint blockade, the designed UCMS@Pep-aPDL1 successfully potentiated local and systemic antitumor immunity and reduced the progression of metastatic foci, demonstrating a synergistic strategy for cancer immunotherapy.https://doi.org/10.1186/s12951-021-00975-5Spine metastasisPeptide vaccineImmunogenic cell deathPhotodynamic therapyProgrammed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) blockades |
| spellingShingle | Zhenqing Wang Liang Chen Yiqun Ma Xilei Li Annan Hu Huiren Wang Wenxing Wang Xiaomin Li Bo Tian Jian Dong Peptide vaccine-conjugated mesoporous carriers synergize with immunogenic cell death and PD-L1 blockade for amplified immunotherapy of metastatic spinal Journal of Nanobiotechnology Spine metastasis Peptide vaccine Immunogenic cell death Photodynamic therapy Programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) blockades |
| title | Peptide vaccine-conjugated mesoporous carriers synergize with immunogenic cell death and PD-L1 blockade for amplified immunotherapy of metastatic spinal |
| title_full | Peptide vaccine-conjugated mesoporous carriers synergize with immunogenic cell death and PD-L1 blockade for amplified immunotherapy of metastatic spinal |
| title_fullStr | Peptide vaccine-conjugated mesoporous carriers synergize with immunogenic cell death and PD-L1 blockade for amplified immunotherapy of metastatic spinal |
| title_full_unstemmed | Peptide vaccine-conjugated mesoporous carriers synergize with immunogenic cell death and PD-L1 blockade for amplified immunotherapy of metastatic spinal |
| title_short | Peptide vaccine-conjugated mesoporous carriers synergize with immunogenic cell death and PD-L1 blockade for amplified immunotherapy of metastatic spinal |
| title_sort | peptide vaccine conjugated mesoporous carriers synergize with immunogenic cell death and pd l1 blockade for amplified immunotherapy of metastatic spinal |
| topic | Spine metastasis Peptide vaccine Immunogenic cell death Photodynamic therapy Programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) blockades |
| url | https://doi.org/10.1186/s12951-021-00975-5 |
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