title: A novel oncolytic herpes simplex virus type 2 has potent anti-tumor activity.
abstract: Oncolytic viruses are promising treatments for many kinds of solid tumors. In this study, we constructed a novel oncolytic herpes simplex virus type 2: oHSV2. We investigated the cytopathic effects of oHSV2 in vitro and tested its antitumor efficacy in a 4T1 breast cancer model. We compared its effect on the cell cycle and its immunologic impact with the traditional chemotherapeutic agent doxorubicin. In vitro data showed that oHSV2 infected most of the human and murine tumor cell lines and was highly oncolytic. oHSV2 infected and killed 4T1 tumor cells independent of their cell cycle phase, whereas doxorubicin mainly blocked cells that were in S and G2/M phase. In vivo study showed that both oHSV2 and doxorubicin had an antitumor effect, though the former was less toxic. oHSV2 treatment alone not only slowed down the growth of tumors without causing weight loss but also induced an elevation of NK cells and mild decrease of Tregs in spleen. In addition, combination therapy of doxorubicin followed by oHSV2 increased survival with weight loss than oHSV2 alone. The data showed that the oncolytic activity of oHSV2 was similar to oHSV1 in cell lines examined and in vivo. Therefore, we concluded that our virus is a safe and effective therapeutic agent for 4T1 breast cancer and that the sequential use of doxorubicin followed by oHSV2 could improve antitumor activity without enhancing doxorubicin's toxicity.
authors.affiliation: Department of Pathology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Immunology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Pharmacology, Hubei University of Science and Technology, Xianning, Hubei, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Ning
authors.affiliation: Department of Immunology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Xiufen
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: Department of Pathology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Haizhen
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Pathology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Immunology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Immunology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Immunology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Youhui
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Shuren
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Shangmei
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Immunology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; School of Pharmacology, Hubei University of Science and Technology, Xianning, Hubei, China.
authors.forename: Binlei
authors.initials: B
authors.lastname: Liu
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005818:Genetic Engineering; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D018258:Herpesvirus 2, Human / Q000235:genetics*; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000628:therapy*; D008807:Mice, Inbred BALB C; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*
chemical_list: D000903:Antibiotics, Antineoplastic; D049452:Green Fluorescent Proteins; D004317:Doxorubicin