Anti-bevacizumab idiotype antibody vaccination is effective in inducing VEGF-binding response, impairing tumor outgrowth

Abstract

Tumors require blood supply and, to overcome this restriction, induce angiogenesis. The vascular endothelial growth factor (VEGF) is an important player in this process, which explains the great number of antiangiogenic therapies targeting it. Its relevance culminated with 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 by the use of anti-idiotype (Id) strategy. In the present study, we evaluated the efficacy of an active VEGF-binding immune response generated by anti-bevacizumab idiotype mAb, 10.D7. First of all, the 10.D7 anti-Id mAb vaccination led to detectable levels of VEGF-binding anti-anti-Id antibodies. In order to examine as far this humoral immune response could have implications on 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 studies, mostly 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 relapses. (AU)