title: Combined treatment with anticancer vaccine using genetically modified endothelial cells and imatinib in bladder cancer.
abstract: OBJECTIVE
  We sought to maximize the antitumor effect of an anticancer vaccine based on genetically modified endothelial cells by combining it with the platelet-derived growth factor receptor inhibitor imatinib.
  
  
  METHODS
  Human umbilical vein endothelial cells (HUVECs) were infected with 10 MOI of Ad-CMV-mGMCSF to make anticancer vaccines. One million mouse bladder cancer cells (MBT-2) were subcutaneously inoculated in C3H mice. The experimental groups included the following: Group 1 (phosphate-buffered saline), Group 2 (anticancer vaccine and GM-CSF), Group 3 (imatinib), and Group 4 (anticancer vaccine, GM-CSF, and imatinib). Tumor growth and body weight were measured weekly. At 4 weeks, the tumors were immunostained with anti-CD31, and microvessel density (MVD) was measured. To evaluate the immunological mechanism of each treatment, flow cytometry analysis of activated CD4 and CD8 cells was performed.
  
  
  RESULTS
  At 4 weeks, the mean body weight of each group, excluding the extracted tumor weight, was not significantly different. Since week 3, the mean tumor volume in Group 4 was the smallest among the treatment groups (p<0.05), and a synergistic suppressive effect on tumor volume was observed in Group 4. The MVD in Group 4 was the most suppressed among the treatment groups (p<0.05), and a synergistic anti-angiogenic effect was observed. Flow cytometry analysis revealed that activated CD4+ and CD8+ cells increased in Group 2 and decreased in Group 3 compared with the other groups.
  
  
  CONCLUSIONS
  The combination of genetically modified endothelial cell vaccines and imatinib showed a synergistic antiangiogenic effect in bladder cancer.
authors.affiliation: Department of Urology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Seung Beom
authors.initials: SB
authors.lastname: Ha
authors.forename: Yong Hyun
authors.initials: YH
authors.lastname: Park
authors.forename: Eunhye
authors.initials: E
authors.lastname: Lee
authors.forename: Ja Hyeon
authors.initials: JH
authors.lastname: Ku
authors.forename: Hyeon Hoe
authors.initials: HH
authors.lastname: Kim
authors.forename: Cheol
authors.initials: C
authors.lastname: Kwak