Combined Treatment with Anticancer Vaccine Using Genetically Modified Endothelial Cells and Imatinib in Bladder Cancer.
10.4111/kju.2011.52.5.327
- Author:
Seung Beom HA
1
;
Yong Hyun PARK
;
Eunhye LEE
;
Ja Hyeon KU
;
Hyeon Hoe KIM
;
Cheol KWAK
Author Information
1. Department of Urology, Seoul National University College of Medicine, Seoul, Korea. mdrafael@snu.ac.kr
- Publication Type:Original Article
- Keywords:
Immunotherapy;
Platelet-derived growth factor;
Urinary bladder neoplasms
- MeSH:
Animals;
Benzamides;
Body Weight;
Endothelial Cells;
Flow Cytometry;
Granulocyte-Macrophage Colony-Stimulating Factor;
Human Umbilical Vein Endothelial Cells;
Immunotherapy;
Mice;
Mice, Inbred C3H;
Microvessels;
Piperazines;
Platelet-Derived Growth Factor;
Pyrimidines;
Receptors, Platelet-Derived Growth Factor;
Tumor Burden;
Urinary Bladder;
Urinary Bladder Neoplasms;
Vaccines;
Imatinib Mesylate
- From:Korean Journal of Urology
2011;52(5):327-334
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: 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. MATERIALS AND 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.
