RRC ID 42070
著者 Okaji Y, Tsuno NH, Kitayama J, Saito S, Takahashi T, Kawai K, Yazawa K, Asakage M, Hori N, Watanabe T, Shibata Y, Takahashi K, Nagawa H.
タイトル Vaccination with autologous endothelium inhibits angiogenesis and metastasis of colon cancer through autoimmunity.
ジャーナル Cancer Sci
Abstract Overcoming immune tolerance of tumor angiogenesis should be useful for adjuvant therapy of cancer. We hypothesized that vaccination with autologous endothelium would induce an autoimmune response targeting tumor angiogenesis. To test this concept, we immunized BALB/c mice with a vaccine of glutaraldehyde-fixed murine hepatic sinusoidal endothelial cells (HSEs) in a lung metastasis model of Colon-26 cancer. Vaccination with autologous HSEs induced both preventive and therapeutic anti-tumor immunity that significantly inhibited the development of metastases. ELISA revealed an immunoglobulin response involving IgM and IgG subclasses. These antibodies had a strong affinity for antigens of both murine and human endothelium, and lyzed endothelial cells in the CDC assay. Flow-cytometry and chromium-release cytotoxicity assay revealed a specific CTL response against endothelial cells, which were lyzed in an effector: target ratio-dependent manner. Neither antibodies nor CTLs reacted with Colon-26. The effect of autologous HSEs was more pronounced than that of xenogeneic human umbilical vein endothelial cells (HUVECs), which were tested in the same experimental setting. Our results suggest that vaccination with autologous endothelium can overcome peripheral tolerance of self-angiogenic antigens and therefore should be useful for adjuvant immunotherapy of cancer.
巻・号 95(1)
ページ 85-90
公開日 2004-1-1
DOI 10.1111/j.1349-7006.2004.tb03175.x
PMID 14720332
MeSH Animals Autoantigens / immunology Cancer Vaccines / therapeutic use* Colonic Neoplasms / drug therapy* Colonic Neoplasms / pathology Colonic Neoplasms / prevention & control Cytotoxicity Tests, Immunologic Endothelium / immunology* Female Humans Immunoglobulin G / blood Immunoglobulin M / blood Lung Neoplasms / drug therapy Lung Neoplasms / secondary* Mice Neoplasm Invasiveness Neovascularization, Pathologic / drug therapy* T-Lymphocytes, Cytotoxic / immunology Umbilical Veins / cytology
IF 4.966
引用数 54
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 BALB/3T3 clone A31(RCB0005)