Successful combination of sunitinib and girentuximab in two renal cell carcinoma animal models: a rationale for combination treatment of patients with advanced RCC

Neoplasia : an International Journal for Oncology Research
Jeannette Oosterwijk-WakkaEgbert Oosterwijk

Abstract

Anti-angiogenic treatment with tyrosine kinase inhibitors (TKI) has lead to an impressive increase in progression-free survival for patients with metastatic RCC (mRCC), but mRCC remains largely incurable. We combined sunitinib, targeting the endothelial cells with Girentuximab (monoclonal antibody cG250, recognizing carbonic anhydrase IX (CAIX) targeting the tumor cells to study the effect of sunitinib on the biodistribution of Girentuximab because combination of modalities targeting tumor vasculature and tumor cells might result in improved effect. Nude mice with human RCC xenografts (NU12, SK-RC-52) were treated orally with 0.8 mg/day sunitinib, or vehicle for 7 to 14 days. Three days before start or cessation of treatment mice were injected i.v. with 0.4 MBq/5 μg (111)In-Girentuximab followed by biodistribution studies. Immunohistochemical analyses were performed to study the tumor vasculature and CAIX expression and to confirm Girentuximab uptake. NU12 appeared to represent a sunitinib sensitive tumor: sunitinib treatment resulted in extensive necrosis and decreased microvessel density (MVD). Accumulation of Girentuximab was significantly decreased when sunitinib treatment preceded the antibody injection but remained unchan...Continue Reading

References

Oct 15, 1986·International Journal of Cancer. Journal International Du Cancer·E OosterwijkS O Warnaar
Feb 13, 2004·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Adrienne H BrouwersOtto C Boerman
Jan 12, 2007·The New England Journal of Medicine·Bernard EscudierUNKNOWN TARGET Study Group
Jun 1, 2007·The New England Journal of Medicine·Gary HudesUNKNOWN Global ARCC Trial
Jan 3, 2008·Nature Reviews. Drug Discovery·Claudiu T Supuran
Jan 27, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Cora N SternbergRobert E Hawkins
Apr 7, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Bernard EscudierVesna Sneller
Jun 28, 2011·European Urology·Jean-Jacques PatardJoaquim Bellmunt
Sep 17, 2011·Nature Reviews. Drug Discovery·Dario Neri, Claudiu T Supuran
Nov 8, 2011·European Urology·Guru SonpavdeChristian G Stief
Jun 12, 2012·Cell·Rakesh K Jain, Peter Carmeliet
Dec 6, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Chaitanya R DivgiPaul Russo
Mar 15, 2013·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·J FerlayF Bray
Apr 11, 2013·Drugs·Bernard EscudierGuru Sonpavde
Apr 13, 2013·Cancer Research·Marlous ArjaansElisabeth G E de Vries
May 15, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Rakesh K Jain
Sep 21, 2013·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·A M MolinaR J Motzer
Nov 23, 2013·Cancer Research·Yuhui HuangRakesh K Jain

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Citations

Feb 16, 2016·Expert Opinion on Drug Metabolism & Toxicology·Claudiu T Supuran
Aug 31, 2016·Expert Opinion on Therapeutic Patents·Claudiu T Supuran
Jun 6, 2018·Journal of Enzyme Inhibition and Medicinal Chemistry·Astrid DrenckhanStephanie J Gros
Jul 30, 2020·International Journal of Molecular Sciences·Katarina KoruzaS Zoë Fisher
Nov 30, 2018·Pharmaceuticals·Tais BasacoMatthias Miederer

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Methods Mentioned

BETA
xenograft
xenografts
electrophoresis
PCR

Software Mentioned

Axio vs40
KS400

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