title: Anti-bevacizumab idiotype antibody vaccination is effective in inducing vascular endothelial growth factor-binding response, impairing tumor outgrowth.
abstract: Tumors require blood supply and, to overcome this restriction, induce angiogenesis. Vascular endothelial growth factor (VEGF) plays an important role in this process, which explains the great number of antiangiogenic therapies targeting VEGF. The research and development of targeted therapy has led to the approval of bevacizumab, a humanized anti-VEGF monoclonal antibody (mAb), in clinical settings. However, side effects have been reported, usually as a consequence of bolus-dose administration of the antibody. This limitation could be circumvented through the use of anti-idiotype (Id) antibodies. In the present study, we evaluated the efficacy of an active VEGF-binding immune response generated by an anti-bevacizumab idiotype mAb, 10.D7. The 10.D7 anti-Id mAb vaccination led to detectable levels of VEGF-binding anti-anti-Id antibodies. In order to examine whether this humoral immune response could have implications for tumor development, 10.D7-immunized mice were challenged with B16-F10 tumor cells. Mice immunized with 10.D7 anti-Id mAb revealed reduced tumor growth when compared to control groups. Histological analyses of tumor sections from 10.D7-immunized mice showed increased necrotic areas, decreased CD31-positive vascular density and reduced CD68-positive cell infiltration. Our results encourage further therapeutic studies, particularly if one considers that the anti-Id therapeutic vaccination maintains stable levels of VEGF-binding antibodies, which might be useful in the control of tumor relapse.
authors.affiliation: Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Jéssica de Souza
authors.initials: Jde S
authors.lastname: Sanches
authors.affiliation: Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Rodrigo Barbosa
authors.initials: RB
authors.lastname: de Aguiar
authors.affiliation: Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Carolina Bellini
authors.initials: CB
authors.lastname: Parise
authors.affiliation: Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Juliana Mayumi
authors.initials: JM
authors.lastname: Suzuki
authors.affiliation: Department of Radiology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Roger
authors.initials: R
authors.lastname: Chammas
authors.affiliation: Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Jane Zveiter
authors.initials: JZ
authors.lastname: de Moraes
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D000068258:Bevacizumab / Q000008:administration & dosage / Q000009:adverse effects; D045744:Cell Line, Tumor; D006801:Humans; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
keywords: Angiogenesis; idiotype; monoclonal antibody; vaccination; vascular endothelial growth factor