دورية أكاديمية
Noninvasive Transdermal Administration of mRNA Vaccines Encoding Multivalent Neoantigens Effectively Inhibits Melanoma Growth.
العنوان: | Noninvasive Transdermal Administration of mRNA Vaccines Encoding Multivalent Neoantigens Effectively Inhibits Melanoma Growth. |
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المؤلفون: | Hou Y; Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, China., Wang Z; Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, China., Chen Z; Xuhui District Dental Disease Prevention and Treatment Institute, Shanghai 200030, China., Shuai L; Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, China., Pei Y; Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, China., Sun B; Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, China., Jiang Y; The First Hospital of Jiaxing, Jiaxing Key Laboratory of Virus-related Infectious Diseases, Jiaxing University, Jiaxing 314001, China., Wang H; Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, China. |
المصدر: | ACS biomaterials science & engineering [ACS Biomater Sci Eng] 2024 Jul 08; Vol. 10 (7), pp. 4587-4600. Date of Electronic Publication: 2024 Jun 13. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 101654670 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2373-9878 (Electronic) Linking ISSN: 23739878 NLM ISO Abbreviation: ACS Biomater Sci Eng Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Washington, DC : American Chemical Society, [2015]- |
مواضيع طبية MeSH: | Cancer Vaccines*/immunology , Cancer Vaccines*/administration & dosage , Administration, Cutaneous* , mRNA Vaccines*, Animals ; Mice ; Antigens, Neoplasm/immunology ; Mice, Inbred C57BL ; Female ; Melanoma/therapy ; Melanoma/immunology ; Melanoma/pathology ; Chitosan/chemistry ; Melanoma, Experimental/immunology ; Melanoma, Experimental/therapy ; Melanoma, Experimental/pathology ; Cell Line, Tumor ; RNA, Messenger/genetics ; Skin Neoplasms/immunology ; Skin Neoplasms/therapy ; Skin Neoplasms/pathology ; CD8-Positive T-Lymphocytes/immunology |
مستخلص: | It is difficult to obtain specific tumor antigens, which is one of the main obstacles in the development of tumor vaccines. The vaccines containing multivalent antigens are thought to be more effective in antitumor therapy. In this study, a mRNA encoding three neoantigens of melanoma were prepared and encapsulated into the mannosylated chitosan-modified ethosomes (Eths MC ) to obtain a multivalent mRNA vaccine (MmRV) for transcutaneous immunization (TCI). MmRV can effectively induce maturation of dendritic cells, with a better performance than mRNA of a single neoantigen. TCI patches (TCIPs) loading MmRV or siRNA against PDL1 (siPDL1) were prepared and applied to the skin of melanoma-bearing mice. The results showed that TCIPs significantly increase the levels of TNF-α, IFN-γ, and IL-12 in both plasma and tumor tissues, inhibit tumor growth, as well as promote infiltration of CD 4+ and CD 8+ T cells in the tumor tissues. Furthermore, the combination of MmRV and siPDL1 showed much better antitumor effects than either monotherapy, suggesting a synergistic effect between the vaccine and PDL1 blocker. In addition, the treatment with the TCIPs did not cause damage to the skin, blood, and vital organs of the mice, showing good biosafety. To the best of our knowledge, this work is the first to construct a noninvasive TCI system containing MmRV and siPDL1, providing a convenient and promising approach for tumor treatment. |
فهرسة مساهمة: | Keywords: PDL1; RNA therapy; dendritic cells; melanoma; multivalent antigens; transcutaneous immunization vaccine |
المشرفين على المادة: | 0 (Cancer Vaccines) 0 (mRNA Vaccines) 0 (Antigens, Neoplasm) 9012-76-4 (Chitosan) 0 (RNA, Messenger) |
تواريخ الأحداث: | Date Created: 20240613 Date Completed: 20240708 Latest Revision: 20240708 |
رمز التحديث: | 20240708 |
DOI: | 10.1021/acsbiomaterials.4c00426 |
PMID: | 38869192 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2373-9878 |
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DOI: | 10.1021/acsbiomaterials.4c00426 |