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. 2005 Aug 19;95(1):85–90. doi: 10.1111/j.1349-7006.2004.tb03175.x

Vaccination with autologous endothelium inhibits angiogenesis and metastasis of colon cancer through autoimmunity

Yurai Okaji 1,✉, Nelson Hirokazu Tsuno 1,2, Joji Kitayama 1, Shinsuke Saito 1, Tsuyoshi Takahashi 2, Kazushige Kawai 1, Kentaro Yazawa 1, Masahiro Asakage 1, Nobukazu Hori 1, Toshiaki Watanabe 1, Yoichi Shibata 2, Koki Takahashi 2, Hirokazu Nagawa 1
PMCID: PMC11159040  PMID: 14720332

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 Colon26. The effect of autologous HSEs was more pronounced than that of xenogeneic human umbilical vein endothelial cells (HU‐VECs), 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. (Cancer Sci 2004; 95: 85–90)

Abbreviations:

HSEs

hepatic sinusoidal endothelial cells

HUVECs

human umbilical vein endothelial cells

CTLs

cytotoxic T lymphocytes

CDC

complement‐dependent cytotoxicity

MTS

3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium, inner salt

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