title: Target expression of Staphylococcus enterotoxin A from an oncolytic adenovirus suppresses mouse bladder tumor growth and recruits CD3+ T cell.
abstract: We recently engineered an oncolytic adenovirus (PPE3-SEA) that expresses the superantigen, Staphylococcus enterotoxin A (SEA), and that has enhanced tumor specificity because the telomerase reverse transcriptase and hypoxia-inducible factor promoters regulate expression of E1A and E1B genes, respectively. Here, we evaluated the PPE3-SEA adenovirus anti-tumor activity against MB49 mouse bladder cancer cell proliferation in vitro and in vivo. PPE3-SEA infection of murine MB49 cells in vitro induced cytopathic effects, and significant expression of SEA mRNA and protein, as measured by RT-PCR and western blot, respectively. Subcutaneous MB29 bladder tumors were established in syngeneic C57BL/6 mice. After 10 days, tumors were injected with either oncolytic virus or PBS. Tumor dimensions were measured on days 1, 3, 5, 7, 9, and 11 post-treatment and tumor volumes were calculated. One of eight PPE3-SEA-treated mice had no tumor by day 9. PPE3-SEA treated group had significantly lower mean tumor volume beginning on day 5 post-treatment (p < 0.01), more fibrous tissue in the tumor, and increased presence of infiltrating CD3+ T cells than those of the control group. Gross appearance and histologic sections from the livers and kidneys of the PPE3-SEA-treated group were similar to those of the control group. In conclusion, oncolytic adenoviruses can provide a novel delivery vehicle for SEA to tumor sites, and PPE3-SEA warrants further study as a potential anti-tumor agent for bladder cancer.
authors.affiliation: Department of Urology, The Affiliated School of Clinical Medicine of Xuzhou Medical College, Xuzhou Central Hospital, 199 Jie Fang Nan Road, Xuzhou, 221009, People's Republic of China.
authors.forename: Conghui
authors.initials: C
authors.lastname: Han
authors.forename: Lin
authors.initials: L
authors.lastname: Hao
authors.forename: Meng
authors.initials: M
authors.lastname: Chen
authors.forename: Jianpeng
authors.initials: J
authors.lastname: Hu
authors.forename: Zhenduo
authors.initials: Z
authors.lastname: Shi
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Bingzheng
authors.initials: B
authors.lastname: Dong
authors.forename: Yu
authors.initials: Y
authors.lastname: Fu
authors.forename: Changsong
authors.initials: C
authors.lastname: Pei
authors.forename: Yongping
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D017252:CD3 Complex / Q000378:metabolism; D045744:Cell Line, Tumor; D048430:Cell Shape; D002470:Cell Survival; D004768:Enterotoxins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D005260:Female; D015870:Gene Expression; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D018089:Superantigens / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D047368:Tumor Burden; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*
chemical_list: D001426:Bacterial Proteins; D017252:CD3 Complex; D004768:Enterotoxins; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal