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

Author:

Lee Seonghyun12ORCID,Yoon Hyunho12,Hong Seol Hee34,Kwon Sung Pil5,Hong Jung Joo67,Kwak Hye Won8,Park Hyeong‐Jun8,Yoo Soyeon5,Bae Seo‐Hyeon12,Park Hyo‐Jung12,Lee Jisun1,Bang Yoo‐Jin18,Lee Yu‐Sun12,Kim Jae‐Yong18,Yoon Subin12,Roh Gahyun12,Cho Youngran12,Kim Yongkwan8,Kim Daegeun8,Park Sang‐In8,Kim Do‐Hyung18,Lee Sowon1,Oh Ayoung12,Ha Dahyeon12,Lee Soo‐Yeon12,Park Misung12,Hwang Eun‐Ha6,Bae Gyuseo6,Jeon Eunsu6,Park Sung Hyun6,Choi Won Seok6,Oh Ho Rim9,Kim In Woo9,Youn Hyewon910,Keum Gyochang5,Bang Eun‐Kyoung5,Rhee Joon Haeng11,Lee Shee Eun34,Nam Jae‐Hwan12ORCID

Affiliation:

1. Department of Medical and Biological Sciences The Catholic University of Korea Bucheon Gyeonggi‐do South Korea

2. BK21 four Department of Biotechnology The Catholic University of Korea Bucheon Gyeonggi‐do South Korea

3. National Immunotherapy Innovation Center Hwasun‐gun Jeonnam South Korea

4. Department of Pharmacology and Dental Therapeutics, School of Dentistry Chonnam National University Gwangju South Korea

5. Brain Science Institute Korea Institute of Science and Technology Seoul South Korea

6. National Primate Research Center Korea Research Institute of Bioscience and Biotechnology (KRIBB) Cheongju Chungcheongbuk‐do South Korea

7. KRIBB School of Bioscience Korea University of Science & Technology (UST) Daejeon South Korea

8. R&D Research Center SML Biopharm Gwangmyeong Gyeonggi‐do South Korea

9. Cancer Research Institute Seoul National University College of Medicine Seoul South Korea

10. Department of Nuclear Medicine, Cancer Imaging Center Seoul National University Hospital Seoul South Korea

11. Department of Microbiology Chonnam National University Medical School Hwasun‐gun Jeonnam South Korea

Abstract

AbstractThe 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.

Funder

Korea Health Industry Development Institute

Ministry of Food and Drug Safety

National Research Foundation of Korea

Korea Centers for Disease Control and Prevention

Korea Research Institute of Bioscience and Biotechnology

Korea Institute of Science and Technology

National Research Council of Science and Technology

Publisher

Wiley

Subject

Infectious Diseases,Virology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3