Heil, FlorianBabitzki, GalinaJulien-Laferriere, AliceOoi, Chia-HueyHidalgo, ManuelMassard, ChristopheMartinez-García, MariaLe Tourneau, ChristopheKockx, MarkGerber, PeterRossomanno, SimonaKrieter, OliverLahr, AngelikaWild, NorbertVega Harring, SuzanaLechner, Katharina2022-02-252022-02-252021Heil F, Babitzki G, Julien-Laferriere A, Ooi CH, Hidalgo M, Massard C, et al. Vanucizumab mode of action: serial biomarkers in plasma, tumor, and skin-wound-healing biòpsies. Transl Oncol. 2021 Feb; 14(2): 100984. DOI: 10.1016/j.tranon.2020.1009841936-5233http://hdl.handle.net/10230/52575Vanucizumab is a novel bispecific antibody inhibiting vascular endothelial growth factor (VEGF-A) and angiopoietin-2 (Ang-2) that demonstrated safety and anti-tumor activity in part I of a phase I study of 42 patients with advanced solid tumors. Part II evaluated the pharmacodynamic effects of vanucizumab 30 or 15 mg/kg every 2 weeks in 32 patients. Serial plasma samples, paired tumor, and skin-wound-healing biopsies were taken over 29 days to evaluate angiogenic markers. Vanucizumab was associated with marked post-infusion reductions in circulating unbound VEGF-A and Ang-2. By day 29, tumor samples revealed mean reductions in density of microvessels (-32.2%), proliferating vessels (-47.9%) and Ang-2 positive vessels (-62.5%). Skin biopsies showed a mean reduction in density of microvessels (-49.0%) and proliferating vessels (-25.7%). Gene expression profiling of tumor samples implied recruitment and potential activation of lymphocytes. Biopsies were safely conducted. Vanucizumab demonstrated a consistent biological effect on vascular-related biomarkers, confirming proof of concept. Skin-wound-healing biopsies were a valuable surrogate for studying angiogenesis-related mechanisms.application/pdfengCopyright © 2020 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).info:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.tranon.2020.100984Angiopoietin-2BiomarkersMicro vessel densityMode of actionPhase I clinical trialVanucizumabinfo:eu-repo/semantics/openAccess