title: Dendritic cells serve as a "Trojan horse" for oncolytic adenovirus delivery in the treatment of mouse prostate cancer.
abstract: OBJECTIVE
  Adenovirus-mediated gene therapy is a novel therapeutic approach for the treatment of cancer, in which replication of the virus itself is the anticancer method. However, the success of this novel therapy is limited due to inefficient delivery of the virus to the target sites. In this study, we used dendritic cells (DCs) as carriers for conditionally replicating adenoviruses (CRAds) in targeting prostate carcinoma (PCa).
  
  
  METHODS
  Four types of CRAds, including Ad-PC (without PCa-specific promoter and a recombinant human tumor necrosis factor, rmhTNF, sequence), Ad-PC-rmhTNF (without PCa-specific promoter), Ad-PPC-NCS (without an rmhTNF sequence) and Ad-PPC-rmhTNF, were constructed. The androgen-insensitive mouse PCa RM-1 cells were co-cultured with CRAd-loading DCs, and the viability of RM-1 cells was examined using MTT assay. The in vivo effects of CRAd-loading DCs on PCa were evaluated in RM-1 xenograft mouse model.
  
  
  RESULTS
  Two PCa-specific CRAds (Ad-PPC-NCS, Ad-PPC-rmhTNF) exhibited more potent suppression on the viability of RM-1 cells in vitro than the PCa-non-specific CRAds (Ad-PC, Ad-PC-rmhTNF). In PCa-bearing mice, intravenous injection of the PCa-specific CRAd-loading DCs significantly inhibited the growth of xenografted tumors, extended the survival time, and induced T-cell activation. Additionally, the rmhTNF-containing CRAds exhibited greater tumor killing ability than CRAds without rmhTNF.
  
  
  CONCLUSIONS
  DCs may be an effective vector for the delivery of CRAds in the treatment of PCa.
authors.affiliation: Department of Urology, the Second Affiliated Hospital, Xi-an Jiaotong University Medical College, Xi-an 710004, China.
authors.forename: Zhao-Lun
authors.initials: ZL
authors.lastname: Li
authors.affiliation: Department of Oncology, the First Affiliated Hospital, Xi-an Jiaotong University Medical College, Xi-an 710061, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Urology, the Second Affiliated Hospital, Xi-an Jiaotong University Medical College, Xi-an 710004, China.
authors.forename: He-Cheng
authors.initials: HC
authors.lastname: Li
authors.affiliation: Department of Urology, the Second Affiliated Hospital, Xi-an Jiaotong University Medical College, Xi-an 710004, China.
authors.forename: Zi-Ming
authors.initials: ZM
authors.lastname: Wang
authors.affiliation: Department of Urology, the Second Affiliated Hospital, Xi-an Jiaotong University Medical College, Xi-an 710004, China.
authors.forename: Tie
authors.initials: T
authors.lastname: Chong
mesh_terms: D000256:Adenoviridae / Q000502:physiology*; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D003713:Dendritic Cells / Q000821:virology*; D004337:Drug Carriers / Q000627:therapeutic use; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008297:Male; D051379:Mice; D050130:Oncolytic Virotherapy / Q000379:methods*; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D014409:Tumor Necrosis Factor-alpha