Korean J Urol.  2011 May;52(5):327-334.

Combined Treatment with Anticancer Vaccine Using Genetically Modified Endothelial Cells and Imatinib in Bladder Cancer

• Ha SB
• Park YH
• Lee E
• Ku JH
• Kim HH
• Kwak C

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.

Keyword

Immunotherapy; Platelet-derived growth factor; Urinary bladder neoplasms

MeSH Terms

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
Benzamides
Granulocyte-Macrophage Colony-Stimulating Factor
Piperazines
Platelet-Derived Growth Factor
Pyrimidines
Receptors, Platelet-Derived Growth Factor
Vaccines