Initial testing (stage 1) of mapatumumab (HGS-ETR1) by the pediatric preclinical testing program.

Abstract

Mapatumumab (HGS-ETR1) is a fully human IgG1 agonistic monoclonal antibody that exclusively targets and activates tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1). It was tested in vitro at concentrations from 0.01 to 100 microg/ml and in vivo at a dose of 10 mg/kg administered intraperitoneally using a twice-weekly schedule. Mapatumumab demonstrated limited activity against the 23 cell lines of the PPTP in vitro panel with no lines achieving 50% growth inhibition. Mapatumumab induced significant differences in event-free survival distribution compared to controls in 9 of 37 evaluable solid tumor xenografts tested, but in none of the 8 ALL xenografts.

• Authors: Malcolm A Smith, Christopher L Morton, E Anders Kolb, Richard Gorlick, Stephen T Keir, Hernan Carol, Richard Lock, Min H Kang, C Patrick Reynolds, John M Maris, Amy E Watkins, Peter J Houghton
• Journal: Pediatric blood & cancer (Pediatr Blood Cancer) Vol. 54 Issue 2 Pg. 307-10 (Feb 2010) ISSN: 1545-5017 [Electronic] United States
• PMID: 19856388 (Publication Type: Evaluation Study, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: (c) 2009 Wiley-Liss, Inc.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• mapatumumab

Topics

• Animals
• Antibodies, Monoclonal (pharmacology, toxicity)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents (pharmacology, toxicity)
• Cell Line, Tumor
• Drug Evaluation, Preclinical
• Female
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, SCID
• Pediatrics
• Receptors, TNF-Related Apoptosis-Inducing Ligand (agonists)
• Survival Analysis
• Xenograft Model Antitumor Assays