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

Pediatr Blood Cancer. 2010 Feb;54(2):307-10. doi: 10.1002/pbc.22188.

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.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / toxicity
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / 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

Substances

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