Skip to main content
main-content

01.03.2012 | Original Article | Ausgabe 3/2012

Cancer Chemotherapy and Pharmacology 3/2012

Pharmacodynamics of DT-IgG, a dual-targeting antibody against VEGF-EGFR, in tumor xenografted mice

Zeitschrift:
Cancer Chemotherapy and Pharmacology > Ausgabe 3/2012
Autoren:
Selwyn J. Hurwitz, Hongzheng Zhang, Sujin Yun, Thil D. Batuwangala, Michael Steward, Steve D. Holmes, Daniel Rycroft, Lin Pan, Mourad Tighiouart, Hyung Ju C. Shin, Lydia Koenig, Yuxiang Wang, Zhuo (Georgia) Chen, Dong M. Shin
Wichtige Hinweise
Selwyn J. Hurwitz and Hongzheng Zhang contributed equally to this work.
Domantis Limited is a wholly owned subsidiary of GlaxoSmithKline.

Abstract

Purpose

DT-IgG is a fully humanized dual-target therapeutic antibody being developed to simultaneously target epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), important signaling molecules for tumor growth. The antitumor pharmacodynamics (PD) of DT-IgG was studied in nude mice bearing human tumor xenografts with different EGFR and VEGF expressions and K-ras oncogene status and compared with bevacizumab, cetuximab and bevacizumab + cetuximab.

Methods

Mice bearing human oral squamous cell carcinoma (Tu212), lung adenocarcinoma (A549), or colon cancer (GEO) subcutaneous xenografts were administered with the antibodies intraperitoneally (i.p.), and tumor volumes were measured versus time. Nonlinear mixed effects modeling (NONMEM) was used to study drug potencies (IC50) and variations in tumor growth.

Results

The PD models adequately described tumor responses for the antibody dose regimens. In vivo IC50 values varied with EGFR and K-ras status. DT-IgG had a similar serum t 1/2 as cetuximab (~1.7 vs. 1.5 day), was more rapid than bevacizumab (~6 day), and had the largest apparent distribution volume (DT-IgG > cetuximab > bevacizumab). The efficacy of DT-IgG was comparable to bevacizumab despite lower serum concentrations, but was less than bevacizumab + cetuximab.

Conclusions

A lower IC50 of DT-IgG partially compensated for lower serum concentrations than bevacizumab and cetuximab, but may require higher doses for comparable efficacy as the combination. The model adequately predicted variations of tumor response at the DT-IgG doses tested and could be used for targeting specific tumor efficacies for future testing.

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

★ PREMIUM-INHALT
e.Med Interdisziplinär

Für Ihren Erfolg in Klinik und Praxis - Die beste Hilfe in Ihrem Arbeitsalltag als Mediziner*in

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf SpringerMedizin.de.

Jetzt e.Med zum Sonderpreis bestellen!
Das Angebot gilt nur bis 24.10.2021

Weitere Produktempfehlungen anzeigen
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 3/2012

Cancer Chemotherapy and Pharmacology 3/2012 Zur Ausgabe
  1. Sie können e.Med Innere Medizin 14 Tage kostenlos testen (keine Print-Zeitschrift enthalten). Der Test läuft automatisch und formlos aus. Es kann nur einmal getestet werden.

Neu im Fachgebiet Onkologie

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Onkologie und bleiben Sie gut informiert – ganz bequem per eMail.

Bildnachweise