Nawa Akihiro, Luo ChenHong, Zhang Lumin, Ushjima Yoko, Ishida Daisuke, Kamakura Maki, Fujimoto Yasushi, Goshima Fumi, Kikkawa Fumitaka, Nishiyama Yukihiro
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Curr Gene Ther. 2008 Jun;8(3):208-21. doi: 10.2174/156652308784746422.
Oncolytic HSV-1 has been developed as a novel anticancer agent. According to the properties and functions of HSV-1 encoded proteins, several genes have been targeted for engineering of oncolytic HSV-1. As a result, a variety of strategies have been applied to the engineering of oncolytic HSV-1. Success in cancer therapy for solid tumors requires a maximal oncolytic effect; however, recombinant HSV-1 that has been adapted to meet neurotoxicity requirements for the treatment of brain tumors may be too highly attenuated for effective use in solid tumors outside the brain. Recently, there has been renewed interest in the high potency of naturally oncolytic viruses. In this review, we will overview the engineered oncolytic HSV developed thus far, as well as its mechanism of selectivity and its mode of spreading within tumors. We also discuss the preclinical and clinical studies of HF-10, a non-engineered oncolytic HSV-1 virus, and its potential for use in cancer gene therapy.
溶瘤性单纯疱疹病毒1型(HSV-1)已被开发为一种新型抗癌药物。根据HSV-1编码蛋白的特性和功能,几个基因已成为溶瘤性HSV-1工程改造的靶点。因此,多种策略已应用于溶瘤性HSV-1的工程改造。实体瘤癌症治疗的成功需要最大程度的溶瘤效果;然而,为满足脑肿瘤治疗的神经毒性要求而改造的重组HSV-1可能因过度减毒而无法有效地用于脑外实体瘤。最近,人们对天然溶瘤病毒的高效性重新产生了兴趣。在这篇综述中,我们将概述迄今为止开发的工程化溶瘤性HSV,以及其选择性机制和在肿瘤内的传播方式。我们还将讨论非工程化溶瘤性HSV-1病毒HF-10的临床前和临床研究,以及其在癌症基因治疗中的应用潜力。