[A DNA vaccine encoding the extracellular domain of porcine endoglin induces antitumor immunity in a mouse colon carcinoma model].
OBJECTIVE
Endoglin is a marker of tumor angiogenesis. Increasing evidences proved that passive immunotherapy with anti-endoglin monoclonal antibody can effectively inhibit tumor growth, and xenogeneic homologous DNA vaccine can inhibit cross antitumor immunity. This study was to explore the inhibitory effect of a DNA vaccine encoding the extracellular domain of porcine endoglin (ppEDG) on tumor growth in a mouse colon carcinoma model.


METHODS
ppEDG was used as a DNA vaccine to actively immunize the colon carcinoma-bearing mice. Tumor volume and survival rate of the mice were observed in 3-day intervals. Microvessel density (MVD) was detected by immunohistochemistry; antibodies against self-endoglin were detected by Western blot and ELISA; the B cells that secrete auto-antibodies against self-endoglin were detected by ELISPOT assay.


RESULTS
Eighteen days after tumor cell inoculation, the tumor volume was significantly smaller in ppEDG-immunized group than in empty plasmid (e-p) group and normal saline (NS) group (P<0.05), and the survival time was significantly longer in ppEDG-immunized group than in the control groups (P<0.001). MVD was significantly lower in ppEDG-immunized group than in e-p group and NS group (19.2+/-4.5 vs. 76.9+/-14.4 and 81.4+/-16.9, P<0.001). The antibodies against self-endoglin were identified in ppEDG-immunized group; the major subtypes were IgG(1) and IgG(2b). The auto-antibody-producing B cells were much more in ppEDG-immunized group than in e-p group and NS group (82.5+/-14.1 vs. 3.6+/-1.3 and 4.7+/-2.0, P<0.001).


CONCLUSIONS
ppEDG DNA vaccine could induce the production of auto-antibodies against self-endoglin, which further inhibit angiogenesis and growth of colon carcinoma.
Jiao
Jie-Ge
JG
Hepatobiliary and Enteric Surgical Research Center of Health Ministry, Center South University, Changsha, Hunan, P. R. China.
Zhang
Yang-De
YD
Li
Yue-Nan
YN
D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D001323:Autoantibodies / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology; D019556:COS Cells / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003110:Colonic Neoplasms / Q000098:blood supply / Q000276:immunology / Q000473:pathology*; D000071063:Endoglin; D005260:Female; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D010957:Plasmids; D011956:Receptors, Cell Surface / Q000235:genetics*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D015703:Antigens, CD; D001323:Autoantibodies; D019496:Cancer Vaccines; C064206:ENG protein, human; D000071063:Endoglin; D007074:Immunoglobulin G; D011956:Receptors, Cell Surface; D019444:Vaccines, DNA