Anti-tumor effects of a human VEGFR-2-based DNA vaccine in mouse models.

Abstract

BACKGROUND:

Vascular endothelial growth factor (VEGF) and its receptor, VEGFR-2 (Flk-1/KDR), play a key role in tumor angiogenesis. Blocking the VEGF-VEGFR-2 pathway may inhibit tumor growth. Here, we used human VEGFR-2 as a model antigen to explore the feasibility of immunotherapy with a plasmid DNA vaccine based on a xenogeneic homologue of this receptor.

METHODS:

The protective effects and therapeutic anti-tumor immunity mediated by the DNA vaccine were investigated in mouse models. Anti-angiogenesis effects were detected by immunohistochemical staining and the alginate-encapsulate tumor cell assay. The mechanism of action of the DNA vaccine was primarily explored by detection of auto-antibodies and CTL activity.

RESULTS:

The DNA vaccine elicited a strong, protective and therapeutic anti-tumor immunity through an anti-angiogenesis mechanism in mouse models, mediated by the stimulation of an antigen-specific response against mFlk-1.

CONCLUSION:

Our study shows that a DNA vaccine based on a xenogeneic homologue plasmid DNA induced autoimmunity against VEGFR-2, resulting in inhibition of tumor growth. Such vaccines may be clinically relevant for cancer immunotherapy.

• Authors: Ke Xie, Rui-Zhen Bai, Yang Wu, Quan Liu, Kang Liu, Yu-Quan Wei
• Journal: Genetic vaccines and therapy (Genet Vaccines Ther) Vol. 7 Pg. 10 (Jun 21 2009) ISSN: 1479-0556 [Electronic] England
• PMID: 19545394 (Publication Type: Journal Article)