Immunogenicity and effectiveness of an mRNA therapeutic vaccine for HPV-related malignancies
© 2024 Wang et al..
Human papillomavirus (HPV) infections account for several human cancers. There is an urgent need to develop therapeutic vaccines for targeting preexisting high-risk HPV (such as HPV 16 and 18) infections and lesions, which are insensitive to preventative vaccines. In this study, we developed a lipid nanoparticle-formulated mRNA-based HPV therapeutic vaccine (mHTV), mHTV-02, targeting the E6/E7 of HPV16 and HPV-18. mHTV-02 dramatically induced antigen-specific cellular immune response and robust memory T-cell immunity in mice, besides significant CD8+ T-cell infiltration and cytotoxicity in TC-1 tumors expressing HPV E6/E7, resulting in tumor regression and prolonged survival in mice. Moreover, evaluation of routes of administration found that intramuscular or intratumoral injection of mHTV-02 displayed significant therapeutic effects. In contrast, intravenous delivery of the vaccine barely showed any benefit in reducing tumor size or improving animal survival. These data together support mHTV-02 as a candidate therapeutic mRNA vaccine via specific administration routes for treating malignancies caused by HPV16 or HPV18 infections.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
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| Enthalten in: |
Life science alliance - 7(2024), 6 vom: 21. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Jing [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 25.03.2024 published: Electronic-Print Citation Status MEDLINE |
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| doi: |
10.26508/lsa.202302448 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Human papillomavirus (HPV) infections account for several human cancers. There is an urgent need to develop therapeutic vaccines for targeting preexisting high-risk HPV (such as HPV 16 and 18) infections and lesions, which are insensitive to preventative vaccines. In this study, we developed a lipid nanoparticle-formulated mRNA-based HPV therapeutic vaccine (mHTV), mHTV-02, targeting the E6/E7 of HPV16 and HPV-18. mHTV-02 dramatically induced antigen-specific cellular immune response and robust memory T-cell immunity in mice, besides significant CD8+ T-cell infiltration and cytotoxicity in TC-1 tumors expressing HPV E6/E7, resulting in tumor regression and prolonged survival in mice. Moreover, evaluation of routes of administration found that intramuscular or intratumoral injection of mHTV-02 displayed significant therapeutic effects. In contrast, intravenous delivery of the vaccine barely showed any benefit in reducing tumor size or improving animal survival. These data together support mHTV-02 as a candidate therapeutic mRNA vaccine via specific administration routes for treating malignancies caused by HPV16 or HPV18 infections | ||
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| 700 | 1 | |a Chen, Yunfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Rui |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Qixin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Tingting |e verfasserin |4 aut | |
| 700 | 1 | |a Yi, Dongrong |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Qian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yongxin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Weiguo |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Yijie |e verfasserin |4 aut | |
| 700 | 1 | |a Cen, Shan |e verfasserin |4 aut | |
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