REBACIN® inhibits E6/E7 oncogenes in clearance of human papillomavirus infection

Shu-Guang Zhou; Dai-Fei Wu; Hui Yao; Wei-Yu Zhang; Feng-Jiao Tian; Guo Chen; Chun-Fa Zhang

doi:10.3389/fonc.2022.1047222

REBACIN^® inhibits E6/E7 oncogenes in clearance of human papillomavirus infection

Front Oncol. 2022 Dec 6:12:1047222. doi: 10.3389/fonc.2022.1047222. eCollection 2022.

Authors

Shu-Guang Zhou¹, Dai-Fei Wu², Hui Yao¹, Wei-Yu Zhang¹, Feng-Jiao Tian³, Guo Chen¹, Chun-Fa Zhang²

Affiliations

¹ Department of Gynecology, Anhui Medical University Affiliated Maternity and Child Healthcare Hospital, Anhui Province Maternity and Child Healthcare Hospital, Hefei, Anhui, China.
² Division of Molecular Virology, SR Life Sciences Institute, Clarksburg, MD, United States.
³ Key Laboratory of Protein Engineering and Drug Development of Hainan, Haikou, China.

Abstract

Previous studies have demonstrated that REBACIN^® intervention eliminates persistent high-risk human papillomavirus (hrHPV) infection. The initial establishment and subsequent progression of cervical cancer mainly depends on two major oncogenes, E6/E7, and previous studies have proposed E6/E7 oncogenes as a target for therapeutic drug development. The aim of this study was to investigate in vitro and in vivo whether REBACIN^® inhibits E6/E7 oncogenes for elucidating the mechanism of REBACIN^® in the clearance of persistent hrHPV infection. In vitro, after REBACIN^® treatment, the growth of both Ca Ski and HeLa cervical cancer cells containing the E6/E7 oncogenes was prevented. In line with this finding is that E6/E7 expression was inhibited, which can be counteracted by the co-application of anti-REBACIN^® antibody. These studies demonstrated that REBACIN^® can effectively inhibit the growth of cervical cancer cells via targeting HPV E6/E7 expression. To further verify this finding in clinic, 108 volunteer patients with persistent hrHPV infections were randomly divided into REBACIN^®, recombinant human interferon alpha-2b (Immunological drug control), or no-treatment blank control groups, received intravaginal administration of REBACIN^®, interferon or no-treatment every other day for three months, and then followed up for E6/E7 mRNA assay. In REBACIN^® group, 68.57% of patients showed complete clearance of HPV E6/E7 mRNA, which was significantly higher compared to 25.00% in the interferon immunological drug control group and 20.00% in blank control group, confirming that REBACIN^® is potently efficacious on clearing persistent hrHPV infections via inhibition of HPV E6/E7 oncogenes.

Clinical trial registration: http://www.chictr.org.cn/historyversionpuben.aspx?regno=ChiCTR2100045911, identifier ChiCTR2100045911.

Keywords: E6/E7; REBACIN; cervical cancer; clearance; human papilloma virus (HPV).