Non-Engineered, Naturally Oncolytic Herpes Simplex Virus HSV1 HF-10:Applications for Cancer Gene Therapy

Akihiro      Nawa; ChenHong      Luo; Lumin      Zhang; Yoko      Ushjima; Daisuke      Ishida; Maki      Kamakura; Yasushi      Fujimoto; Fumi      Goshima; Fumitaka      Kikkawa; Yukihiro      Nishiyama

doi:10.2174/156652308784746422

Abstract

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.

Keywords: Gene therapy for cancer, solid tumors outside of the brain, engineered oncolytic virus, non-engineered and naturally occurring HSV1 HF10, PKR signaling pathway, activation of immune system, HSV amplicon system, carrier cell strategy