Active Immunization Against the Vascular Endothelial Growth Factor Receptor flk1 Inhibits Tumor Angiogenesis and Metastasis

• DOI: 10.1084/jem.20020072
• Publication Date: 2002-07-26T16:48:54Z
• Authors: Yiwen Li; Mei-Nai Wang; Hongli Li; Karen D. King; Rajiv Bassi; Haijun Sun; Angel Santiago; Andrea T. Hooper; Peter Bohlen; Daniel J. Hicklin
• Keywords: Lewis lung carcinoma; Active immunization

The vascular endothelial growth factor (VEGF) receptor fetal liver kinase 1 (flk1; VEGFR-2, KDR) is an cell–specific tyrosine that mediates physiological and pathological angiogenesis. We hypothesized active immunotherapy approach targeting flk1 may inhibit tumor angiogenesis metastasis. To test this hypothesis, we first evaluated whether immune responses to could be elicited in mice by immunization with dendritic cells pulsed a soluble protein (DC-flk1). This generated flk1-specific neutralizing antibody CD8+ cytotoxic T cell responses, breaking tolerance self-flk1 antigen. Tumor-induced was suppressed immunized as measured alginate bead assay. Development of pulmonary metastases strongly inhibited DC-flk1–immunized challenged B16 melanoma or Lewis lung carcinoma cells. DC-flk1 also significantly prolonged the survival tumors. Thus, strategy targets angiogenesis-related antigen on endothelium can useful for treating diseases.