Blocking FGF2 with a new specific monoclonal antibody impairs angiogenesis and experimental metastatic melanoma, suggesting a potential role in adjuvant settings

Author(s)

de Aguiar, Rodrigo Barbosa ^{[1, 2]} ; Parise, Carolina Bellini ^[2] ; Teixeira Souza, Carolina Rosal ^[1] ; Braggion, Camila ^[2] ; Quintilio, Wagner ^[3] ; Moro, Ana Maria ^[3] ; Navarro Marques, Fabio Luiz ^[4] ; Buchpiguel, Carlos Alberto ^[4] ; Chammas, Roger ^[1] ; de Moraes, Jane Zveiter ^[2]

Affiliation

^[1] Univ Sao Paulo, Fac Med, Dept Radiol & Oncol, Ave Dr Arnaldo 251, BR-01246000 Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, Escola Paulista Med, Dept Biofis, Rua Botucatu 862, BR-04023062 Sao Paulo - Brazil

^[3] Inst Butantan, Lab Biofarm Celulas Anim, Ave Vital Brasil 1500, BR-05503900 Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Fac Med, Ctr Med Nucl, Trav Rua Dr Ovidio Pires Campos S-N, BR-05403010 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Cancer Letters; v. 371, n. 2, p. 151-160, 2016.
• Web of Science Citations: 9

Abstract

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. (AU)

• FAPESP's process: 09/18631-1 - STUDY OF ANTIBODIES FOR INHIBITION OF ANGIOGENESIS IN MELANOMA
• Grantee: Jane Zveiter de Moraes
• Support Opportunities: Regular Research Grants
• FAPESP's process: 98/14247-6 - Center for Research on Cell-Based Therapy
• Grantee: Marco Antonio Zago
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 13/06120-8 - Modulation of tumor perfusion as a strategy to improve the distribution of chemotherapeutic drugs in a melanoma model
• Grantee: Roger Chammas
• Support Opportunities: Regular Research Grants