title: Enhanced antitumor efficacy of integrin-targeted oncolytic adenovirus AxdAdB3-F/RGD on bladder cancer.
abstract: OBJECTIVE
  To evaluate the therapeutic efficacy of AxdAdB-3 with Arg-Gly-Asp (RGD)-fiber modification (AxdAdB3-F/RGD), which enables integrin-dependent infection in bladder cancers.
  
  
  METHODS
  Flow cytometric analysis was applied to evaluated adenovirus-mediated gene transduction into various cells. The cytopathic effects of AxdAdB3-F/RGD were evaluated in bladder cancer cell lines and a normal bladder mucosa-derived cell line (HCV29) with AxCAZ3-F/RGD (control) or AxdAdB-3. The efficacy of bladder instillation therapy with AxdAdB3-F/RGD for orthotopic bladder cancer was investigated in nude mice.
  
  
  RESULTS
  Expression of coxsackievirus adenovirus receptor (CAR) and integrins (αvβ3 and αvβ5) vary in different bladder cancer cell lines. The susceptibility of various cell lines to adenovirus was associated with the expression of CAR. AxdAdB-3 was more cytopathic in CAR-positive bladder cancer cells than in CAR-negative cells, whereas AxdAdB3-F/RGD caused effective oncolysis in both CAR-positive and CAR-negative bladder cancer cells. AxdAdB3-F/RGD was not cytotoxic to HCV29 cells. Direct instillation of AxdAdB3-F/RGD into the bladder of the orthotopic model, established by CAR-deficient human bladder cancer cells, inhibited tumor growth and led to significantly elongated survival.
  
  
  CONCLUSIONS
  E1A and E1B double-restricted oncolytic adenovirus with RGD fiber modification has enhanced infectivity and oncolytic effects to CAR-deficient bladder cancers, suggesting the therapeutic potential of AxdAdB3-F/RGD for bladder cancers.
authors: Department of Urology, Zhejiang Cancer Hospital, Hangzhou, China. Electronic address: hwangua@aliyun.com.
authors: Hua
authors: H
authors: Wang
authors: Institute of Immunology, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Zhijian
authors: Z
authors: Cai
authors: Institute of Immunology, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Fei
authors: F
authors: Yang
authors: Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, China.
authors: Juan
authors: J
authors: Luo
authors: Department of Urology, Sen-en General Hospital, Tagajo, Miyagi, Japan.
authors: Makoto
authors: M
authors: Satoh
authors: Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Yoichi
authors: Y
authors: Arai
authors: Department of Urology, Zhejiang Cancer Hospital, Hangzhou, China.
authors: Dechuan
authors: D
authors: Li
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D016023:Integrins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000627:therapeutic use*; D011991:Receptors, Virus / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D016023:Integrins; D009842:Oligopeptides; D011991:Receptors, Virus; C085301:adenovirus receptor; C047981:arginyl-glycyl-aspartic acid