Vaccination with xenogeneic tumor endothelial proteins isolated in situ inhibits tumor angiogenesis and spontaneous metastasis.
Angiogenesis is critical for tumor growth and metastasis. Tumor tissues induce the expression of angiogenesis-associated proteins on endothelial surface that can be targeted for tumor immunotherapy. In our study, the rat tumor endothelial proteins (EP) were isolated in situ via biotinylation of tumor vascular endothelial luminal surface followed by streptavidin affinity chromatography. The isolated tumor EP contained numerous up-regulated angiogenesis-associated endothelial proteins. The administration of these tumor EP as a vaccine to mice reduced the microvessel density in subcutaneous primary LLC tumors, delayed spontaneous LLC tumor metastasis and prolonged post-surgery life span. T lymphocytes from tumor EP-vaccinated mice lysed human umbilical vascular endothelial cells, but not tumor cells in vitro, in a dose-dependent manner. Furthermore, adoptive transfer of antitumor EP antibodies in vivo targeted to tumor endothelium and inhibited spontaneous LLC tumor metastasis. This study provides a successful preclinical exploration of the active immunotherapy for tumor by targeting tumor angiogenesis.
Zhang
Wang
W
Institute of Molecular Medicine and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
Liu
Jian-Ning
JN
Tan
Xiang-Yang
XY
D000230:Adenocarcinoma / Q000098:blood supply*; D019264:Adoptive Transfer; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D019921:Biotinylation; D018827:Carcinoma, Lewis Lung / Q000098:blood supply*; D002465:Cell Movement; D015180:Electrophoresis, Gel, Two-Dimensional; D004730:Endothelium, Vascular / Q000737:chemistry*; D005260:Female; D005434:Flow Cytometry; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000098:blood supply*; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply*; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000627:therapeutic use*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344; D014611:Vaccination
D020533:Angiogenesis Inhibitors; D007074:Immunoglobulin G; D009363:Neoplasm Proteins