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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Immunogenicity and effectiveness of an mRNA therapeutic vaccine for HPV-related malignancies
Jing Wang1, Ling Ma1, Yunfeng Chen2
1Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China.
Abstract:
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.
Insights
A novel mRNA therapeutic vaccine (mHTV-02) effectively targets high-risk HPV infections. Intramuscular or intratumoral delivery demonstrated significant tumor regression and improved survival in preclinical models.
Area of Science:
- Oncology
- Immunology
- Vaccinology
Background:
- Human papillomavirus (HPV) infections are linked to numerous cancers.
- Existing preventative vaccines are ineffective against pre-existing high-risk HPV (16 and 18) infections and lesions.
- Therapeutic vaccines are crucial for treating HPV-driven malignancies.
Purpose of the Study:
- To develop and evaluate a lipid nanoparticle-formulated mRNA-based HPV therapeutic vaccine (mHTV-02).
- To assess mHTV-02's efficacy against HPV16 and HPV18 E6/E7 oncoproteins.
- To determine optimal administration routes for mHTV-02 therapy.
Main Methods:
- Development of mHTV-02, an mRNA vaccine targeting HPV16/18 E6/E7.
- Assessment of immune responses, including T-cell infiltration and cytotoxicity, in a TC-1 tumor mouse model.
- Comparison of therapeutic effects following intramuscular, intratumoral, and intravenous administration.
Main Results:
- mHTV-02 induced strong antigen-specific cellular and memory T-cell immunity in mice.
- Significant CD8+ T-cell infiltration and cytotoxicity were observed in TC-1 tumors.
- Intramuscular and intratumoral injections led to tumor regression and prolonged survival.
- Intravenous delivery showed minimal therapeutic benefit.
Conclusions:
- mHTV-02 demonstrates potent anti-tumor activity against HPV16/18-driven cancers.
- Specific administration routes (intramuscular, intratumoral) are critical for vaccine efficacy.
- mHTV-02 is a promising therapeutic mRNA vaccine candidate for HPV-associated malignancies.
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