dc.contributor.author | Baker, LCJ | |
dc.contributor.author | Boult, JKR | |
dc.contributor.author | Thomas, M | |
dc.contributor.author | Koehler, A | |
dc.contributor.author | Nayak, T | |
dc.contributor.author | Tessier, J | |
dc.contributor.author | Ooi, C-H | |
dc.contributor.author | Birzele, F | |
dc.contributor.author | Belousov, A | |
dc.contributor.author | Zajac, M | |
dc.contributor.author | Horn, C | |
dc.contributor.author | LeFave, C | |
dc.contributor.author | Robinson, SP | |
dc.date.accessioned | 2016-09-06T14:26:53Z | |
dc.date.issued | 2016-09-06 | |
dc.identifier.citation | British journal of cancer, 2016, 115 (6), pp. 691 - 702 | |
dc.identifier.issn | 0007-0920 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/103 | |
dc.identifier.eissn | 1532-1827 | |
dc.identifier.doi | 10.1038/bjc.2016.236 | |
dc.description.abstract | BACKGROUND: To assess antivascular effects, and evaluate clinically translatable magnetic resonance imaging (MRI) biomarkers of tumour response in vivo, following treatment with vanucizumab, a bispecific human antibody against angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A). METHODS: Colo205 colon cancer xenografts were imaged before and 5 days after treatment with a single 10 mg kg(-1) dose of either vanucizumab, bevacizumab (anti-human VEGF-A), LC06 (anti-murine/human Ang-2) or omalizumab (anti-human IgE control). Volumetric response was assessed using T2-weighted MRI, and diffusion-weighted, dynamic contrast-enhanced (DCE) and susceptibility contrast MRI used to quantify tumour water diffusivity (apparent diffusion coefficient (ADC), × 10(6) mm(2) s(-1)), vascular perfusion/permeability (K(trans), min(-1)) and fractional blood volume (fBV, %) respectively. Pathological correlates were sought, and preliminary gene expression profiling performed. RESULTS: Treatment with vanucizumab, bevacizumab or LC06 induced a significant (P<0.01) cytolentic response compared with control. There was no significant change in tumour ADC in any treatment group. Uptake of Gd-DTPA was restricted to the tumour periphery in all post-treatment groups. A significant reduction in tumour K(trans) (P<0.05) and fBV (P<0.01) was determined 5 days after treatment with vanucizumab only. This was associated with a significant (P<0.05) reduction in Hoechst 33342 uptake compared with control. Gene expression profiling identified 20 human genes exclusively regulated by vanucizumab, 6 of which are known to be involved in vasculogenesis and angiogenesis. CONCLUSIONS: Vanucizumab is a promising antitumour and antiangiogenic treatment, whose antivascular activity can be monitored using DCE and susceptibility contrast MRI. Differential gene expression in vanucizumab-treated tumours is regulated by the combined effect of Ang-2 and VEGF-A inhibition. | |
dc.format | Print-Electronic | |
dc.format.extent | 691 - 702 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line, Tumor | |
dc.subject | Animals | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Adenocarcinoma | |
dc.subject | Colonic Neoplasms | |
dc.subject | Neovascularization, Pathologic | |
dc.subject | Angiogenesis Inhibitors | |
dc.subject | Angiopoietin-2 | |
dc.subject | Vascular Endothelial Growth Factor A | |
dc.subject | Immunoglobulin E | |
dc.subject | Antibodies, Bispecific | |
dc.subject | Antibodies, Monoclonal | |
dc.subject | Magnetic Resonance Imaging | |
dc.subject | Tumor Burden | |
dc.subject | Xenograft Model Antitumor Assays | |
dc.subject | Gene Expression Profiling | |
dc.subject | DNA Replication | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.subject | Molecular Targeted Therapy | |
dc.subject | Antibodies, Monoclonal, Humanized | |
dc.subject | Bevacizumab | |
dc.subject | Omalizumab | |
dc.title | Acute tumour response to a bispecific Ang-2-VEGF-A antibody: insights from multiparametric MRI and gene expression profiling. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-07-06 | |
rioxxterms.versionofrecord | 10.1038/bjc.2016.236 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2016-09 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | British journal of cancer | |
pubs.issue | 6 | |
pubs.notes | No embargo | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Magnetic Resonance | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Magnetic Resonance | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI | |
pubs.publication-status | Published | |
pubs.volume | 115 | |
pubs.embargo.terms | No embargo | |
pubs.oa-location | http://www.nature.com/bjc/journal/vaop/ncurrent/pdf/bjc2016236a.pdf | |
icr.researchteam | Magnetic Resonance | |
icr.researchteam | Pre-Clinical MRI | |
dc.contributor.icrauthor | Baker, Lauren | |
dc.contributor.icrauthor | Boult, Jessica | |
dc.contributor.icrauthor | Robinson, Simon | |