Vanucizumab mode of action: serial biomarkers in plasma, tumor, and skin-wound-healing biopsies

Heil, Florian; Babitzki, Galina; Julien-Laferriere, Alice; Ooi, Chia-Huey; Hidalgo, Manuel; Massard, Christophe; Martinez-García, Maria; Le Tourneau, Christophe; Kockx, Mark; Gerber, Peter; Rossomanno, Simona; Krieter, Oliver; Lahr, Angelika; Wild, Norbert; Vega Harring, Suzana; Lechner, Katharina

Vanucizumab mode of action: serial biomarkers in plasma, tumor, and skin-wound-healing biopsies

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dc.contributor.author Heil, Florian
dc.contributor.author Babitzki, Galina
dc.contributor.author Julien-Laferriere, Alice
dc.contributor.author Ooi, Chia-Huey
dc.contributor.author Hidalgo, Manuel
dc.contributor.author Massard, Christophe
dc.contributor.author Martinez-García, Maria
dc.contributor.author Le Tourneau, Christophe
dc.contributor.author Kockx, Mark
dc.contributor.author Gerber, Peter
dc.contributor.author Rossomanno, Simona
dc.contributor.author Krieter, Oliver
dc.contributor.author Lahr, Angelika
dc.contributor.author Wild, Norbert
dc.contributor.author Vega Harring, Suzana
dc.contributor.author Lechner, Katharina
dc.date.accessioned 2022-02-25T07:37:40Z
dc.date.available 2022-02-25T07:37:40Z
dc.date.issued 2021
dc.description.abstract Vanucizumab 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.
dc.format.mimetype application/pdf
dc.identifier.citation Heil 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.2020.100984
dc.identifier.doi http://dx.doi.org/10.1016/j.tranon.2020.100984
dc.identifier.issn 1936-5233
dc.identifier.uri http://hdl.handle.net/10230/52575
dc.language.iso eng
dc.publisher Elsevier
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.keyword Angiopoietin-2
dc.subject.keyword Biomarkers
dc.subject.keyword Micro vessel density
dc.subject.keyword Mode of action
dc.subject.keyword Phase I clinical trial
dc.subject.keyword Vanucizumab
dc.title Vanucizumab mode of action: serial biomarkers in plasma, tumor, and skin-wound-healing biopsies
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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