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Blood, 15 September 2005, Vol. 106, No. 6, pp. 2026-2032.
Prepublished online as a Blood First Edition Paper on May 26, 2005; DOI 10.1182/blood-2005-03-0969.
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Submitted March 11, 2005
Accepted May 17, 2005
T cell-mediated suppression of angiogenesis results in tumor protective immunity
He Zhou, Yunping Luo, Masato Mizutani, Noriko Mizutani, Ralph A Reisfeld, and Rong Xiang*
Department of Immunology, The Scripps Research Institute, La Jolla, CA, USA
* Corresponding author; email: rxiang{at}scripps.edu.
Anti-angiogenic intervention is known to inhibit tumor growth and dissemination by attacking the tumor vascular supply. Here, we report that this was achieved for the first time using an oral DNA minigene vaccine against murine vascular endothelial growth factor receptor-2 (FLK-1), a self-antigen overexpressed on proliferating endothelial cells in the tumor vasculature. Moreover, we identified the first H-2Db-restricted epitope, FLK400 (VILTNPISM), specifically recognized by CTLs. Such CTLs were capable of killing FLK-1+ endothelial cells, resulting in suppression of angiogenesis and long-lived tumor protection. The specificity of this immune response was indicated as the DNA vaccine encoding the entire FLK-1 gene also induced a FLK400-specific CTL response. This minigene vaccine strategy provides a more flexible alternative to whole gene vaccination and facilitates in depth mechanism studies to tailor DNA vaccines for optimal T cell activation and tumor protection.

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