Earticle

초록

영어

The proapoptotic tumor necrosis factor–related apoptosis inducing ligand (TRAIL) receptors death
receptor (DR) 4 and DR5 are attractive targets to develop the receptorspecificagonistic monoclonal
antibodies (mAb) as anticancer agents because of their tumor-selective cell death–inducing
activity. Here, we report a novel agonistic mAb, AY4, raised against human DR4 in mice. ELISA
analysis revealed that AY4 specifically bound to DR4 withoutcompetition with TRAIL for the
binding. Despite distinct binding regions of AY4 on DR4 from those of TRAIL, AY4 as a single
agent induced caspase-dependent apoptotic cell death of several tumor types through the extrinsic and/or intrinsic pathways without substantial cytotoxicity to normal human hepatocytes. Further, the AY4-sensitive cells followed the same cell death characteristics classified as type I and type II cells by the response to TRAIL,suggesting that the cell death profiles in responses to DR4 and/or DR5 stimulation are determined by the downstream signaling of the receptor rather than the kind of receptor. Noticeably, AY4 efficiently induced cell death of Jurkat cells, which have been reported to be resistant to other anti-DR4 agonistic mAbs, most likely due to the unique epitope property of AY4. In vivo administration of AY4 significantly inhibited tumor growth of human non–small cell lung carcinoma preestablished in athymic nude mice. Conclusively, our results provide further insight into the DR4-mediated cell death signaling and potential use of AY4 mAb as an anticancer therapeutic agent, particularly for DR4-responsive tumor types.

키워드

저자

• Eun-Sil SUNG [ Department of Molecular Science and Technology, Ajou University ]
• Kyung-Jin PARK [ Department of Molecular Science and Technology, Ajou University ]
• Seung-Hyun LEE [ Department of Molecular Science and Technology, Ajou University ]
• Yoon-Seon JANG [ Biotech Laboratory, Yuhan Research Institute, Yuhan Corporation, Yongin 446-902. ]
• Sang-Koo PARK [ Biotech Laboratory, Yuhan Research Institute, Yuhan Corporation, Yongin 446-902. ]
• Yoo-Hoi PARK [ Biotech Laboratory, Yuhan Research Institute, Yuhan Corporation, Yongin 446-902. ]
• Won-Jae KWAG [ Biotech Laboratory, Yuhan Research Institute, Yuhan Corporation, Yongin 446-902. ]
• Myung-Hee KWON [ Department of Microbiology, Ajou University School of Medicine, Suwon 442-721. ]
• Yong-Sung KIM [ Department of Molecular Science and Technology, Ajou University, Suwon 443-749. ]

참고문헌

발행기관

간행물

표지보기 관심저널 등록

• 간행물명

  한국생물공학회 학술대회

• 간기

  반년간

• 수록기간

  1985~2013

• 십진분류

  KDC 476 DDC 576