Br. J. Cancer
HGS-ETR1, a fully human TRAIL-receptor 1 monoclonal antibody, induces cell death in multiple tumor types in vitro and in vivo.
Pukac, L., Kanakaraj, P., Humphreys, R., Alderson, R., Bloom, M., Sung, C., Riccobene, T., Johnson, R., Fiscella, M., Mahoney, A., Carrell, J., Boyd, E., Yao, X.T., Zhang, L., Zhong, L., von Kerczek, A., Shepard, L., Vaughan, T., Edwards, B., Dobson, C., Salcedo, T. and Albert, V.
Notes: The authors examine and characterize HGS-ETR1 (Mapatumumab), a fully human agonistic monoclonal antibody with high affinity and specificity for TRAIL-R1. HGS-ETR1 induced cell death in tumor cell lines was mediated by the activation of the extrinsic and intrinsic death signaling pathways. The tumor cell lines Colo205, HCT116, H460, H2122, ST486, SW480, RL95-2, WU.86.86, ES2, A498, WM793, SNU398, JURL-MKI and TTn were plated at 10,000 cells/well in 96-well white, opaque plates. The tumor cells were treated with the HGS-ETR1 or a isotope control antibody (ICmAB). After 48 hours, cell viability was determined by the CellTiter-Glo® Luminescent Cell Viability Assay. Luminescence was detected using a Northstar luminescent plate reader. Caspase 3/7 activity was assessed in the HGS-ETR1 and ICmAB treated tumor cells using the Apo-ONE™ Homogeneous Caspase-3/7 Assay. The cells were plated at 10,000 cells/well into black-walled 96-well plates and treated with the HGS-ETR1 and ICmAB for 6 hours at 37°C. Caspase activity was measured by reading the plates at 405nm using a fluorometric plate reader. (3314)
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