Is death receptor 4 or 5 a good traget for cancer antibody therapy?
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL),a member of the tumor necrosis factor super-family,induces cell death upon binding to its death receptors (DR4 and DR5) via an intrinsic and/or an extrinsic signaling pathway.Promisingly,DR4 or DR5 preferentially mediates cell death in various cancer cells without toxicity to most normal cells.These unique characters of death receptors lead to the development death receptor-targeting cancer therapeutics,including the agonistic antibodies against DR4 or DR5.There have been several antibodies against DR4 or DR5 in clinical trials exhibiting a promising foreground.We present here the preclinical study of a novel anti-DR5 monoclonal antibody,AD5-10,which induces cell death in various tumor cells in the absence of second cross-linking antibody in vitro and a strong tumoricidal activity in vivo.AD5-10 does not compete with its native ligand TRAIL for binding to DR5,but contrarily synergizes with TRAIL to induce cell death in various cancer cells.Preclinical study demonstrated that the remodeled antibodies (scFv,chimeric and humanized as well as viral expressed antibody) of AD5-10 showed a strong cytotoxicity to the cancer cells of liver,lung,colon,leukemia,breast and ovary both in vitro and in vivo.These data indicate that remodeled antibody of AD5-10 could be a promising therapeutic for cancers.
Zheng De-xian Liu Yan-xin
Institute of Basic Medical Sciences,Chinses Academy of Medical Sciences
国内会议
三亚
英文
153-153
2012-11-16（万方平台首次上网日期，不代表论文的发表时间）