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Immunotherapy of tumors with xenogeneic endothelial cells as a vaccine

Abstract

The breaking of immune tolerance against autologous angiogenic endothelial cells should be a useful approach for cancer therapy. Here we show that immunotherapy of tumors using fixed xenogeneic whole endothelial cells as a vaccine was effective in affording protection from tumor growth, inducing regression of established tumors and prolonging survival of tumor-bearing mice. Furthermore, autoreactive immunity targeting to microvessels in solid tumors was induced and was probably responsible for the anti-tumor activity. These observations may provide a new vaccine strategy for cancer therapy through the induction of an autoimmune response against the tumor endothelium in a cross-reaction.

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Acknowledgements

This work was supported by the National Outstanding Young Scientist Foundation of China, the National Natural Sciences Foundation of China, the National 973 Project and the Foundation for University Key Teacher.

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Correspondence to Yu-quan Wei.

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Figure 1: Induction of protective anti-tumor immunity.
Figure 2: Induction of the therapeutic anti-tumor immunity.
Figure 3: The inhibition of proliferation of endothelial cells in vitro with immunoglobulin.
Figure 4: Adoptive transfer of immunoglobulins in vivo.
Figure 5: In situ observation of microvessels and inhibition of angiogenesis.
Figure 6: Abrogation of the anti-tumor activity and immunoglobulin subclass response to the endothelial cells by the depletion of CD4+ T lymphocytes.
Figure 7: Identification of the possible antigens responsible for the cross-reaction.