Administration of a liposomal FGF-2 peptide vaccine leads to abrogation ofFGF-2-mediated angiogenesis and tumor development

Basic fibroblast growth factor (FGF-2) is an important stimulator of angiog enesis that has been implicated in neoplastic progression. Attempts to neut ralize or modulate FGF-2 have met with some success in controlling neovascu larity and tumor growth. In the present study, two peptides: one correspond ing to the heparin binding domain and the other to the receptor binding dom ain of FGF-2, exerted dose-dependent inhibition of FGF-2-stimulated human u mbilical vein endothelial cell proliferation (IC50 = 70 and 20 mug/ml, resp ectively). The identification of these functional regions suggested that ta rgeting these domains might be an approach for the modulation of FGF-2 func tion. To investigate this possibility, we vaccinated mice with either the h eparin binding domain peptide or the receptor binding domain peptide of FGF -2 in a liposome/adjuvant format, and analyzed the effect of vaccination on FGF-2-driven angiogenesis, tumor development and immune status. Mice vacci nated with the heparin binding domain peptide generated a specific antibody response to FGF-2, blocked neovascularization in a gelfoam sponge model of angiogenesis, and inhibited experimental metastasis by > 90% in two tumor models: the B16BL6 melanoma and the Lewis lung carcinoma. These effects wer e not observed in mice treated with the receptor binding domain peptide con jugated to liposomes or liposomes lacking conjugated peptide. These data su ggest that a heparin binding domain peptide of FGF-2, when presented to a h ost in a liposomal adjuvant formulation, can ultimately lead to inhibition of angiogenesis and tumor growth. (C) 2000 Elsevier Science Ltd. All rights reserved.