Novel Anticancer Vaccine Using Genetically Modified Endothelial Cells

Jeong, Hyeon; Kwak, Cheol; Park, Moon Soo; Lee, Sang Eun

Abstract

PURPOSE: Immunotherapy with tumor cell vaccines has shown limited success in established tumors, for reasons including suppressed expression of MHC molecules or absent tumor associated antigens, and active production of immunosuppressive molecules of tumor cells. The development of a vaccine targeting tumor angiogenesis might overcome the limitation of tumor cell vaccines.
MATERIALS AND METHODS
Human umbilical vein endothelial cells(HUVEC) were infected with 20MOI of Ad-CMV-mGMCSF, and GM-CSF expression was measured by ELISA assay. One million mouse bladder cancer cells (MBT-2) were subcutaneously inoculated in C3H mice. The growth of tumors was measured after weekly intraperitoneal injection of saline(group I), HUVEC cells(group II), and HUVEC cells infected with Ad-CMV- mGMCSF(group III). At 4 weeks, the tumors were immunostained with anti-CD31 and the microvessel density(MVD) was measured. To evaluate the mechanism of this vaccine, flow cytometry analysis for activated CD4 and CD8 was performed.
RESULTS
The mean expression of GM-CSF was 215ng/106 HUVEC cells at 24 hours after infection. There was no significant difference in tumor growth between groups I and II. However, the tumor growth in group III was significantly suppressed compared to that in groups I and II(p<0.05), as was MVD(p<0.05). In flow cytometry analysis, activated CD4 and CD8 cells were increased in group III compared to those of groups I and II.
CONCLUSIONS
GM-CSF producing endothelial cell vaccine suppressed the growth of established bladder tumors, which may be explained by specific T cell mediated immune reaction to the tumor angiogenesis.