The characteristic of an anti-human DR5 antibody A6.
The efficacy of many cancer treatments is due to their ability to induce apoptosis. DR5 can activate apoptosis pathway after binding with its natural ligand, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L). Both TRAIL and agonistic anti-DR5 monoclonal antibody are currently being explored for cancer therapy. The mechanisms of cytotoxicity of our previously prepared monoclonal antibody A6 against DR5 were investigated here. A6 could cause viability loss of Jurkat cells in both time- and dose-dependent manner which could be attributed to the activation of apoptosis pathway. Caspases 3, 8 and 9 were activated in Jurkat cells and the caspase specific inhibitors, such as broad caspases inhibitor Z-VAD-FMK, caspase 8 specific inhibitor Z-IETD-FMK and caspase 9 specific inhibitor Z-LEHD-FMK could recover the viability loss caused by A6. The function and molecular mechanism of TRAIL-mediated apoptosis were also investigated and compared with those of A6. Although A6 and TRAIL recognize a different epitope, they could induce a similar reaction in Jurkat cells.
Wang
Yu Gang
YG
Institute of Basic Medical Sciences, Beijing, China.
Zhao
Kui Peng
KP
Chen
Ju Gao
JG
Zhang
Ji Yan
JY
Yu
Ming
M
Li
Yan
Y
Shen
Bei Fen
BF
D000590:Amino Acid Chloromethyl Ketones / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D009842:Oligopeptides / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000819:agonists / Q000276:immunology* / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000276:immunology / Q000378:metabolism*
D000590:Amino Acid Chloromethyl Ketones; D000911:Antibodies, Monoclonal; D061945:Caspase Inhibitors; D009842:Oligopeptides; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C403753:benzyloxycarbonyl-isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone; C403754:benzyloxycarbonyl-leucyl-glutamyl-histidyl-aspartic acid fluoromethyl ketone; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases