Prevention and treatment of HPV-related cancer through a mRNA vaccine expressing APC-targeting antigen
© 2024 John Wiley & Sons Ltd..
Persistent human papillomavirus (HPV) infection is associated with multiple malignancies. Developing therapeutic vaccines to eliminate HPV-infected and malignant cells holds significant value. In this study, we introduced a lipid nanoparticle encapsulated mRNA vaccine expressing tHA-mE7-mE6. Mutations were introduced into E6 and E7 of HPV to eliminate their tumourigenicity. A truncated influenza haemagglutinin protein (tHA), which binds to the CD209 receptor on the surface of dendritic cells (DCs), was fused with mE7-mE6 in order to allow efficient uptake of antigen by antigen presenting cells. The tHA-mE7-mE6 (mRNA) showed higher therapeutic efficacy than mE7-mE6 (mRNA) in an E6 and E7+ tumour model. The treatment resulted in complete tumour regression and prevented tumour formation. Strong CD8+ T-cell immune response was induced, contributing to preventing and curing of E6 and E7+ tumour. Antigen-specific CD8+ T were found in spleens, peripheral blood and in tumours. In addition, the tumour infiltration of DC and NK cells were increased post therapy. In conclusion, this study described a therapeutic mRNA vaccine inducing strong anti-tumour immunity in peripheral and in tumour microenvironment, holding promising potential to treat HPV-induced cancer and to prevent cancer recurrence.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Immunology - (2024) vom: 12. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Xiaoxuan [VerfasserIn] |
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| Links: |
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| Themen: |
Haemagglutinin (HA) |
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| Anmerkungen: |
Date Revised 12.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1111/imm.13777 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369613805 |
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| 520 | |a Persistent human papillomavirus (HPV) infection is associated with multiple malignancies. Developing therapeutic vaccines to eliminate HPV-infected and malignant cells holds significant value. In this study, we introduced a lipid nanoparticle encapsulated mRNA vaccine expressing tHA-mE7-mE6. Mutations were introduced into E6 and E7 of HPV to eliminate their tumourigenicity. A truncated influenza haemagglutinin protein (tHA), which binds to the CD209 receptor on the surface of dendritic cells (DCs), was fused with mE7-mE6 in order to allow efficient uptake of antigen by antigen presenting cells. The tHA-mE7-mE6 (mRNA) showed higher therapeutic efficacy than mE7-mE6 (mRNA) in an E6 and E7+ tumour model. The treatment resulted in complete tumour regression and prevented tumour formation. Strong CD8+ T-cell immune response was induced, contributing to preventing and curing of E6 and E7+ tumour. Antigen-specific CD8+ T were found in spleens, peripheral blood and in tumours. In addition, the tumour infiltration of DC and NK cells were increased post therapy. In conclusion, this study described a therapeutic mRNA vaccine inducing strong anti-tumour immunity in peripheral and in tumour microenvironment, holding promising potential to treat HPV-induced cancer and to prevent cancer recurrence | ||
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| 700 | 1 | |a Wang, Huiyan |e verfasserin |4 aut | |
| 700 | 1 | |a Lai, Wujiang |e verfasserin |4 aut | |
| 700 | 1 | |a Liao, Jinrong |e verfasserin |4 aut | |
| 700 | 1 | |a Mo, Wenyu |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Keke |e verfasserin |4 aut | |
| 700 | 1 | |a He, Liqing |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Xiaomei |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Zhibin |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Jiang |e verfasserin |4 aut | |
| 700 | 1 | |a Hua, Xianwu |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Fujun |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, William Wei-Guo |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Kuan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yifeng |e verfasserin |4 aut | |
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