Disease: Human papillomavirus (HPV) related cervical cancer, (NCT02800369)

Disease info:

Human Papillomavirus-HPV persistent infection is the major causal factor of cervical intraepithelial neoplasia (CIN) and cervical cancer.

Genital human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. More than 40 HPV types can infect the genital areas of men and women, including the skin of the penis, vulva (area outside the vagina), and anus, and the linings of the vagina, cervix, and rectum. These types can also infect the lining of the mouth and throat.

HPV types are often referred to as “low-risk” (wart-causing) or “high-risk” (cancer-causing), based on whether they put a person at risk for cancer.  When the body’s immune system can’t get rid of a high-risk HPV infection, it can linger over time and turn normal cells into abnormal cells and then cancer.

Two HPV types (16 and 18) cause 70% of cervical cancers and pre-cancerous cervical lesions.

Frequency:
Approximately 10.900 people are diagnosed with cervical cancer in the US per year.
Official title:
Safety Study of Zinc Finger Nucleases ZFN-602 and ZFN-758 in HPV-infected Subjects.
Who:

Study Director: Hui Wang, M.D. Huazhong University of Science and Technology

Principal Investigator: Wencheng Ding, M.D. Huazhong University of Science and Technology

Principal Investigator: Da Zhu, M.D. Huazhong University of Science and Technology

Partners:
Locations:

China, Hubei

Study start:
Dec. 10, 2016
Enrollment:
20 participants
Gene editing method:
ZFN- Zinc Finger Nucleases
Gene:
HPV16 and HPV18
Vector:
No information
Indicator
IND Enabling Pre-clinical
Phase I Safety
Phase II Safety and Dosing
Phase III Safety and Efficacy

Status: Active not recruiting

Description

Laboratory studies have shown that ZFN-603 and ZFN-758 could induce significant cleavage of E7 DNA in HPV16- and HPV18-positive cells. The disruption to viral DNA directly led to downregulation of E7 expression and restoration of the tumor suppressor genes retinoblastoma 1 (RB1), resulting in apoptosis and growth inhibition of ZFN-treated HPV16- and HPV18- positive cell lines. On the basis of these laboratory results, there is the potential that this may work in humans infected with high-risk HPV (especially HPV16 and HPV18) and block the progression of CIN The new treatment to be studied will involve transfecting ZFNs into HPV-infected cervical epithelials. Cells modified by ZFN-603 and ZFN-758 will lose the ability of immortalization and progress to apoptosis.

Researchers hope that these agents will be able to block the malignant progression of CIN and reduce the incidence of cervical cancer

This research study is being carried out to study a new way to possibly treat human cervical intraepithelial neoplasia (CIN) without invasion.

Persistent infection with specific types of human papillomavirus (HPV, most frequently types 16 and 18) may lead to precancerous lesions(CIN). If untreated, these lesions may progress to cervical cancer within many years. In the infected cells, HPV expresses the oncoproteins E6 and E7, both of which play key roles in maintaining viral infection and promoting carcinogenesis. Previous studies has demonstrated that E7 alone, but not E6, is sufficient to immortalize human keratinocytes in vitro and induce high-grade cervical dysplasia in a transgenic mouse model. These data indicated that E7 may dominate the malignant progress in HPV-infected cells.

The agents zinc finger nucleases (ZFNs), called ZFN-603 and ZFN-758, which can cleave the HPV16 and HPV18 E7 oncogene specifically. ZFN-mediated disruption of HPV16 and HPV18 E7 DNA directly decreased the expression of E7, induced type-specific apoptosis in HPV16- and HPV18-positive cells, and inhibited cell growth.

The purpose of this study is to determine whether ZFN-603 and ZFN-758 are effective in the treatment of HPV16- and HPV18-positive cervical intraepithelial neoplasia.

Last updated: Apr. 30, 2020