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

被引：21

作者：

Lee, Seonghyun ^{[1
,2
]}

Yoon, Hyunho ^{[1
,2
]}

Hong, Seol Hee ^{[3
,4
]}

Kwon, Sung Pil ^{[5
]}

Hong, Jung Joo ^{[6
,7
]}

Kwak, Hye Won ^{[8
]}

Park, Hyeong-Jun ^{[8
]}

Yoo, Soyeon ^{[5
]}

Bae, Seo-Hyeon ^{[1
,2
]}

Park, Hyo-Jung ^{[1
,2
]}

Lee, Jisun ^{[1
]}

Bang, Yoo-Jin ^{[1
,8
]}

Lee, Yu-Sun ^{[1
,2
]}

Kim, Jae-Yong ^{[1
,8
]}

Yoon, Subin ^{[1
,2
]}

Roh, Gahyun ^{[1
,2
]}

Cho, Youngran ^{[1
,2
]}

Kim, Yongkwan ^{[8
]}

Kim, Daegeun ^{[8
]}

Park, Sang-In ^{[8
]}

Kim, Do-Hyung ^{[1
,8
]}

Lee, Sowon ^{[1
]}

Oh, Ayoung ^{[1
,2
]}

Ha, Dahyeon ^{[1
,2
]}

Lee, Soo-Yeon ^{[1
,2
]}

Park, Misung ^{[1
,2
]}

Hwang, Eun-Ha ^{[6
]}

Bae, Gyuseo ^{[6
]}

Jeon, Eunsu ^{[6
]}

Park, Sung Hyun ^{[6
]}

Choi, Won Seok ^{[6
]}

Oh, Ho Rim ^{[9
]}

Kim, In Woo ^{[9
]}

Youn, Hyewon ^{[9
,10
]}

Keum, Gyochang ^{[5
]}

Bang, Eun-Kyoung ^{[5
]}

Rhee, Joon Haeng ^{[11
]}

Lee, Shee Eun ^{[3
,4
,13
]}

Nam, Jae-Hwan ^{[1
,2
,12
]}

机构：

[1] Catholic Univ Korea, Dept Med & Biol Sci, Bucheon, Gyeonggi Do, South Korea

[2] Catholic Univ Korea, BK21 Four Dept Biotechnol, Bucheon, Gyeonggi Do, South Korea

[3] Natl Immunotherapy Innovat Ctr, Hwasun Gun, Jeonnam, South Korea

[4] Chonnam Natl Univ, Sch Dent, Dept Pharmacol & Dent Therapeut, Gwangju, South Korea

[5] Korea Inst Sci & Technol, Brain Sci Inst, Seoul, South Korea

[6] Korea Res Inst Biosci & Biotechnol KRIBB, Natl Primate Res Ctr, Cheongju, Chungcheongbuk, South Korea

[7] Korea Univ Sci & Technol UST, KRIBB Sch Biosci, Daejeon, South Korea

[8] SML Biopharm, R&D Res Ctr, Gwangmyeong, Gyeonggi Do, South Korea

[9] Seoul Natl Univ, Canc Res Inst, Coll Med, Seoul, South Korea

[10] Seoul Natl Univ Hosp, Canc Imaging Ctr, Dept Nucl Med, Seoul, South Korea

[11] Chonnam Natl Univ, Med Sch, Dept Microbiol, Hwasun Gun, Jeonnam, South Korea

[12] Catholic Univ Korea, Dept Med & Biol Sci, 43-1 Yeokgok Dong, Bucheon 14662, South Korea

[13] Chonnam Natl Univ, Sch Dent, Dept Pharmacol & Dent Therapeut, 77 Yongbong Ro, Gwangju 61186, South Korea

来源：

JOURNAL OF MEDICAL VIROLOGY | 2023年 / 95卷 / 12期

基金：

新加坡国家研究基金会;

关键词：

cancer therapy; HPV; HPV-mediated cancer; therapeutic mRNA; vaccine; HUMAN-PAPILLOMAVIRUS; IMMUNE-RESPONSES; TUMOR; IMMUNOTHERAPY; PROTEIN; MICE;

D O I：

10.1002/jmv.29309

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页数：16

共 49 条

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