Initial testing (stage 1) of mapatumumab (HGS-ETR1) by the pediatric preclinical testing program.
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.
Smith
Malcolm A
MA
Cancer Therapy Evaluation Program, NCI, Bethesda, Maryland 20892, USA. smithm@ctep.nic.nih.gov
Morton
Christopher L
CL
Kolb
E Anders
EA
Gorlick
Richard
R
Keir
Stephen T
ST
Carol
Hernan
H
Lock
Richard
R
Kang
Min H
MH
Reynolds
C Patrick
CP
Maris
John M
JM
Watkins
Amy E
AE
Houghton
Peter J
PJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000633:toxicity; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D010372:Pediatrics; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000819:agonists*; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; C507357:mapatumumab