Department of Microbiology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran.
Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Acta Pharmacol Sin. 2021 Dec;42(12):1981-1990. doi: 10.1038/s41401-021-00616-5. Epub 2021 Feb 25.
Although most human papillomavirus (HPV) infections are harmless, persistent infection with high-risk types of HPV is known to be the leading cause of cervical cancer. Following the infection of the epithelium and integration into the host genome, the oncogenic proteins E6 and E7 disrupt cell cycle control by inducing p53 and retinoblastoma (Rb) degradation. Despite the FDA approval of prophylactic vaccines, there are still issues with cervical cancer treatment; thus, many therapeutic approaches have been developed to date. Due to strong immunogenicity, a high capacity for packaging foreign DNA, safety, and the ability to infect a myriad of cells, adenoviruses have drawn attention of researchers. Adenovirus vectors have been used for different purposes, including as oncolytic agents to kill cancer cells, carrier for RNA interference to block oncoproteins expression, vaccines for eliciting immune responses, especially in cytotoxic T lymphocytes (CTLs), and gene therapy vehicles for restoring p53 and Rb function.
虽然大多数人乳头瘤病毒(HPV)感染是无害的,但高危型 HPV 的持续感染已被确认为宫颈癌的主要病因。在感染上皮细胞并整合到宿主基因组后,致癌蛋白 E6 和 E7 通过诱导 p53 和视网膜母细胞瘤(Rb)降解来破坏细胞周期控制。尽管 FDA 批准了预防性疫苗,但宫颈癌的治疗仍存在问题;因此,迄今为止已经开发了许多治疗方法。由于腺病毒具有较强的免疫原性、包装外源 DNA 的大容量、安全性以及感染多种细胞的能力,因此引起了研究人员的关注。腺病毒载体已被用于多种用途,包括作为溶瘤剂来杀死癌细胞、作为 RNA 干扰的载体来阻断致癌蛋白的表达、作为疫苗来引发免疫反应,特别是细胞毒性 T 淋巴细胞(CTL)的免疫反应,以及作为基因治疗载体来恢复 p53 和 Rb 的功能。