Unknown

Dataset Information

0

Anti-EGFL7 antibodies enhance stress-induced endothelial cell death and anti-VEGF efficacy.


ABSTRACT: Many oncology drugs are administered at their maximally tolerated dose without the knowledge of their optimal efficacious dose range. In this study, we describe a multifaceted approach that integrated preclinical and clinical data to identify the optimal dose for an antiangiogenesis agent, anti-EGFL7. EGFL7 is an extracellular matrix-associated protein expressed in activated endothelium. Recombinant EGFL7 protein supported EC adhesion and protected ECs from stress-induced apoptosis. Anti-EGFL7 antibodies inhibited both of these key processes and augmented anti-VEGF-mediated vascular damage in various murine tumor models. In a genetically engineered mouse model of advanced non-small cell lung cancer, we found that anti-EGFL7 enhanced both the progression-free and overall survival benefits derived from anti-VEGF therapy in a dose-dependent manner. In addition, we identified a circulating progenitor cell type that was regulated by EGFL7 and evaluated the response of these cells to anti-EGFL7 treatment in both tumor-bearing mice and cancer patients from a phase I clinical trial. Importantly, these preclinical efficacy and clinical biomarker results enabled rational selection of the anti-EGFL7 dose currently being tested in phase II clinical trials.

SUBMITTER: Johnson L 

PROVIDER: S-EPMC3754254 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications


Many oncology drugs are administered at their maximally tolerated dose without the knowledge of their optimal efficacious dose range. In this study, we describe a multifaceted approach that integrated preclinical and clinical data to identify the optimal dose for an antiangiogenesis agent, anti-EGFL7. EGFL7 is an extracellular matrix-associated protein expressed in activated endothelium. Recombinant EGFL7 protein supported EC adhesion and protected ECs from stress-induced apoptosis. Anti-EGFL7 a  ...[more]

Similar Datasets

| S-EPMC1805509 | biostudies-literature
| S-EPMC3718173 | biostudies-other
| S-EPMC6565989 | biostudies-literature
| S-EPMC3772225 | biostudies-literature
| 2073020 | ecrin-mdr-crc
| S-EPMC3849980 | biostudies-literature
| S-EPMC5691060 | biostudies-literature
| S-EPMC1201157 | biostudies-literature
| S-EPMC5429743 | biostudies-literature
2021-07-28 | GSE160613 | GEO