TY - JOUR
T1 - Vanucizumab mode of action
T2 - Serial biomarkers in plasma, tumor, and skin-wound-healing biopsies
AU - Heil, Florian
AU - Babitzki, Galina
AU - Julien-Laferriere, Alice
AU - Ooi, Chia Huey
AU - Hidalgo, Manuel
AU - Massard, Christophe
AU - Martinez-Garcia, Maria
AU - Le Tourneau, Christophe
AU - Kockx, Mark
AU - Gerber, Peter
AU - Rossomanno, Simona
AU - Krieter, Oliver
AU - Lahr, Angelika
AU - Wild, Norbert
AU - Harring, Suzana Vega
AU - Lechner, Katharina
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2021/2/1
Y1 - 2021/2/1
N2 - 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.
AB - 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.
KW - Angiopoietin-2
KW - Biomarkers
KW - Micro vessel density
KW - Mode of action
KW - Phase I clinical trial
KW - Vanucizumab
UR - http://www.scopus.com/inward/record.url?scp=85097753069&partnerID=8YFLogxK
U2 - 10.1016/j.tranon.2020.100984
DO - 10.1016/j.tranon.2020.100984
M3 - Article
AN - SCOPUS:85097753069
SN - 1936-5233
VL - 14
JO - Translational Oncology
JF - Translational Oncology
IS - 2
M1 - 100984
ER -