title: Destruction of nonimmunogenic mammary tumor cells by a fusogenic oncolytic herpes simplex virus induces potent antitumor immunity.
abstract: In principle, destruction of tumor cells in vivo by oncolytic agents would release the entire repertoire of tumor antigens in their natural forms, leading to effective antitumor immunity. This goal has been elusive despite extensive testing of numerous strategies. We developed a doubly fusogenic oncolytic herpes simplex virus (Synco-2D) that kills tumor cells by a unique dual mechanism combining direct cytolysis with syncytial formation induced by cell membrane fusion. A single intratumor injection of Synco-2D induced strong antitumor immunity against an otherwise nonimmunogenic murine mammary tumor growing in immune-competent mice. CD8+ T cells were the primary mediators of immunity, contributing to the destruction of both primary and metastatic tumors. We conclude that the fusogenic capacity of Synco-2D enables it to elicit antitumor immunity exceeding that induced by more conventional oncolytic viruses.
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Mikihito
authors.initials: M
authors.lastname: Nakamori
authors.forename: Xinping
authors.initials: X
authors.lastname: Fu
authors.forename: Raphael
authors.initials: R
authors.lastname: Rousseau
authors.forename: Si-Yi
authors.initials: SY
authors.lastname: Chen
authors.forename: Xiaoliu
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000276:immunology / Q000821:virology; D002460:Cell Line; D002470:Cell Survival; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D008212:Lymphocyte Depletion; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000821:virology; D008561:Membrane Fusion; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000473:pathology; D009368:Neoplasm Transplantation; D018139:Simplexvirus / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019139:Tumor Escape / Q000276:immunology
chemical_list: D016753:Interleukin-10; D007371:Interferon-gamma