A novel anti-human DR5 monoclonal antibody with tumoricidal activity induces caspase-dependent and caspase-independent cell death.
Like anti-Fas monoclonal antibodies, some monoclonal antibodies against tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors have tumoricidal activity too. In this article we report a novel mouse anti-human DR5 monoclonal antibody, AD5-10, that induces apoptosis of various tumor cell lines in the absence of second cross-linking in vitro and showed strong tumoricidal activity in vivo. AD5-10 does not compete with TRAIL for binding to DR5 and synergizes with TRAIL to induce apoptosis of tumor cells. AD5-10 induces both caspase-dependent and caspase-independent cell death in Jurkat cells, whereas TRAIL induces only caspase-dependent cell death. We show for the first time that DR5 can mediate caspase-independent cell death, and DR5 can mediate distinct cell signals when interacting with different extracellular proteins. Studies on AD5-10 help us to understand more on the functions of DR5 and may provide new ideas for cancer immunotherapy.
Guo
Yabin
Y
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China.
Chen
Caifeng
C
Zheng
Yong
Y
Zhang
Jinchun
J
Tao
Xiaohui
X
Liu
Shilian
S
Zheng
Dexian
D
Liu
Yanxin
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001483:Base Sequence; D015153:Blotting, Western; D020169:Caspases / Q000502:physiology*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D017931:DNA Primers; D016328:NF-kappa B; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; C505639:TNFRSF10B protein, human; C505640:Tnfrsf10b protein, mouse; D020169:Caspases