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. 2023 Dec;95(12):e29309.
doi: 10.1002/jmv.29309.

mRNA-HPV vaccine encoding E6 and E7 improves therapeutic potential for HPV-mediated cancers via subcutaneous immunization

Seonghyun Lee  1   2 , Hyunho Yoon  1   2 , Seol Hee Hong  3   4 , Sung Pil Kwon  5 , Jung Joo Hong  6   7 , Hye Won Kwak  8 , Hyeong-Jun Park  8 , Soyeon Yoo  5 , Seo-Hyeon Bae  1   2 , Hyo-Jung Park  1   2 , Jisun Lee  1 , Yoo-Jin Bang  1   8 , Yu-Sun Lee  1   2 , Jae-Yong Kim  1   8 , Subin Yoon  1   2 , Gahyun Roh  1   2 , Youngran Cho  1   2 , Yongkwan Kim  8 , Daegeun Kim  8 , Sang-In Park  8 , Do-Hyung Kim  1   8 , Sowon Lee  1 , Ayoung Oh  1   2 , Dahyeon Ha  1   2 , Soo-Yeon Lee  1   2 , Misung Park  1   2 , Eun-Ha Hwang  6 , Gyuseo Bae  6 , Eunsu Jeon  6 , Sung Hyun Park  6 , Won Seok Choi  6 , Ho Rim Oh  9 , In Woo Kim  9 , Hyewon Youn  9   10 , Gyochang Keum  5 , Eun-Kyoung Bang  5 , Joon Haeng Rhee  11 , Shee Eun Lee  3   4 , Jae-Hwan Nam  1   2
Affiliations

mRNA-HPV vaccine encoding E6 and E7 improves therapeutic potential for HPV-mediated cancers via subcutaneous immunization

Seonghyun Lee et al. J Med Virol. 2023 Dec.

Abstract

The E6 and E7 proteins of specific subtypes of human papillomavirus (HPV), including HPV 16 and 18, are highly associated with cervical cancer as they modulate cell cycle regulation. The aim of this study was to investigate the potential antitumor effects of a messenger RNA-HPV therapeutic vaccine (mHTV) containing nononcogenic E6 and E7 proteins. To achieve this, C57BL/6j mice were injected with the vaccine via both intramuscular and subcutaneous routes, and the resulting effects were evaluated. mHTV immunization markedly induced robust T cell-mediated immune responses and significantly suppressed tumor growth in both subcutaneous and orthotopic tumor-implanted mouse model, with a significant infiltration of immune cells into tumor tissues. Tumor retransplantation at day 62 postprimary vaccination completely halted progression in all mHTV-treated mice. Furthermore, tumor expansion was significantly reduced upon TC-1 transplantation 160 days after the last immunization. Immunization of rhesus monkeys with mHTV elicited promising immune responses. The immunogenicity of mHTV in nonhuman primates provides strong evidence for clinical application against HPV-related cancers in humans. All data suggest that mHTV can be used as both a therapeutic and prophylactic vaccine.

Keywords: HPV; HPV-mediated cancer; cancer therapy; therapeutic mRNA; vaccine.

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References

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