title: Arg-Gly-Asp (RGD)-Modified E1A/E1B Double Mutant Adenovirus Enhances Antitumor Activity in Prostate Cancer Cells In Vitro and in Mice.
abstract: CAR is a transmembrane protein that is expressed in various epithelial and endothelial cells. CAR mediates adenoviral infection, as well as adenovirus-mediated oncolysis of AxdAdB-3, an E1A/E1B double-restricted oncolytic adenovirus, in prostate cancer cells. This study further assessed the therapeutic efficacy of AxdAdB-3 with Arg-Gly-Asp (RGD)-fiber modification (AxdAdB3-F/RGD), which enables integrin-dependent infection, in prostate cancer. Susceptibility of prostate cancer cells LNCaP, PC3, and DU145 to adenovirus infection was associated with CAR expression. All of the prostate cancer cell lines expressed integrin αvβ3 and αvβ5. AxdAdB-3 was more cytopathic in CAR-positive prostate cancer cells than in CAR-negative cells, whereas AxdAdB3-F/RGD caused potent oncolysis in both CAR-positive and CAR-negative prostate cancer cells. In contrast, AxdAdB3-F/RGD was not cytopathic against normal prostate epithelial cells, RWPE-1. Intratumoral injection of AxdAdB3-F/RGD into CAR-negative prostate cancer cell xenografts in nude mice inhibited tumor growth. The current study demonstrates that E1A/E1B double-restricted oncolytic adenovirus with an RGD-fiber modification enhances infection efficiency and anti-tumor activity in CAR-deficient prostate cancer cells, while sparing normal cells. Future studies will evaluate the therapeutic potential of AxdAdB3-F/RGD in prostate cancer.
authors.affiliation: Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yue-Hong
authors.initials: YH
authors.lastname: Shen
authors.affiliation: Chronic Disease Research Institute, Department of Nutrition, Zhejiang University School of Public Health, School of Medicine, Hangzhou, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Urology, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Immunology, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Zhi-Jian
authors.initials: ZJ
authors.lastname: Cai
authors.affiliation: Department of Urology, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: Yi-Peng
authors.initials: YP
authors.lastname: Xu
authors.affiliation: Department of Urology, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: An
authors.initials: A
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: Gu
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Urology, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: Shao-Xing
authors.initials: SX
authors.lastname: Zhu
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D017500:Adenovirus E1A Proteins / Q000235:genetics*; D017501:Adenovirus E1B Proteins / Q000235:genetics*; D000818:Animals; D045744:Cell Line, Tumor; D003588:Cytopathogenic Effect, Viral; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009154:Mutation; D009842:Oligopeptides / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000473:pathology*
chemical_list: D017500:Adenovirus E1A Proteins; D017501:Adenovirus E1B Proteins; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid