Blocking fgf2 with a new specific monoclonal antibody impairs angiogenesis and experimental metastatic melanoma, suggesting a potential role in adjuvant settings

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de Aguiar, Rodrigo Barbosa [UNIFESP]
Parise, Carolina Bellini [UNIFESP]
Teixeira Souza, Carolina Rosal
Braggion, Camila [UNIFESP]
Quintilio, Wagner
Moro, Ana Maria
Navarro Marques, Fabio Luiz
Buchpiguel, Carlos Alberto
Chammas, Roger
de Moraes, Jane Zveiter [UNIFESP]
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Compelling evidence suggests that fibroblast growth factor 2 (FGF2), overexpressed in melanomas, plays an important role in tumor growth, angiogenesis and metastasis. In this study, we evaluated the therapeutic use of a new anti-FGF2 monoclonal antibody (mAb), 3F12E7, using for that the B16-F10 melanoma model. The FGF2 neutralizing effect of this antibody was certified by in vitro assays, which allowed the further track of its possible in vivo application. 3F12E7 mAb could be retained in B16-F10 tumors, as shown by antibody low-pH elution and nuclear medicine studies, and also led to reduction in number and size of metastatic foci in lungs, when treatment starts one day after intravenous injection of B16-F10 cells. Such data were accompanied by decreased CD34(+) tumor vascular density and impaired subcutaneous tumor outgrowth. Treatments starting one week after melanoma cell intravenous injection did not reduce tumor burden, remaining the therapeutic effectiveness restricted to early-adopted regimens. Altogether, the presented anti-FGF2 3F12E7 mAb stands as a promising agent to treat metastatic melanoma tumors in adjuvant settings. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
Cancer Letters. Clare, v. 371, n. 2, p. 151-160, 2016.