Induction of strong antitumor immunity by an HSV-2-based oncolytic virus in a murine mammary tumor model.
Oncolytic viruses have shown considerable promise for the treatment of solid tumors. In previous studies, we demonstrated that a novel oncolytic virus (FusOn-H2), constructed by replacing the serine/threonine protein kinase (PK) domain of the ICP10 gene of type 2 herpes simplex virus (HSV-2) with the gene encoding the green fluorescent protein, can selectively replicate in and thus lyse tumor cells. 4T1 tumor cells are weakly immunogenic and the mammary tumors derived from them aggressively metastasize to different parts of body, thus providing an attractive model for evaluating anticancer agents. We thus tested the antitumor effect of FusOn-H2 in this tumor model, in comparisons with several other oncolytic HSVs derived from HSV-1, including a nonfusogenic HSV-1 (Baco-1) and a doubly fusogenic virus (Synco-2D). Our results show that FusOn-H2 and Synco-2D have greater oncolytic activity in vitro than Baco-1. Moreover, FusOn-H2 induced strong T cell responses against primary and metastatic mammary tumors in vivo, and splenocytes adoptively transferred from FusOn-H2-treated mice effectively prevented metastasis in naïve mice bearing implanted mammary tumors. We conclude that the HSV-2-based FusOn-H2 oncolytic virus may be an effective agent for the treatment of both primary and metastatic breast cancer.
Li
Hongtao
H
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Dutuor
Aurelie
A
Fu
Xinping
X
Zhang
Xiaoliu
X
D019264:Adoptive Transfer; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D018258:Herpesvirus 2, Human / Q000235:genetics*; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D015674:Mammary Neoplasms, Animal / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
D049452:Green Fluorescent Proteins