title: Immune safety of a novel oncolytic mutant M1 after administration in vivo.
abstract: The aim of this study was to evaluate the safety and efficiency of a novel, oncolytic adenovirus mutant M1 administered in conjunction with immunosuppressive agents. Animal models were established by administering purified M1 either intravenously or retroperitoneally. At different time points, blood samples were taken from the mice for testing of liver and renal function. Microscopic examination of the liver was performed to observe pathological changes. Immunohistochemical analyses were used to evaluate the expression of the adenovirus in the liver. Lymphocyte recruitment to the liver and the activation of adenovirus specific T cells were also analyzed. No signs of general toxicity were observed, but transient increases in ALT and Scr were observed following the administration of M1. Microscopic examination revealed a mild inflammatory response in the liver. Compared to intravenous injection, higher expression levels of adenoviral proteins were observed after retroperitoneal injection. Combined treatment with cyclosporine A resolved the liver and kidney dysfunction and increased the concentration of the adenovirus in the liver. The use of the novel oncolytic adenovirus mutant M1 in vivo is safe, and the combined administration of M1 with immunosuppressive agents was able to enhance the effectiveness and safety profile of M1.
authors.affiliation: Department of Hematology, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Hematology, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Hematology, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Qinlu
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Hematology, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Quanfu
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Department of Hematology, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Hematology, Huazhong University of Science and Technology, Wuhan, 430030, China. caoyangemma@163.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D005260:Female; D007668:Kidney / Q000276:immunology / Q000821:virology; D008099:Liver / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation / Q000235:genetics*