Journal of Pharmaceutical Care & Health Systems
Open Access
ISSN: 2376-0419
ISSN: 2376-0419
Yanru Feng, Hao Yang, Huawei Cai, Dianlong Jia, Heng Li, Ze Tao, Yi Zhong, Zhao Li, Qiuxiao Shi, Lin Wan, Lin Li and Xiaofeng Lu
Sichuan University, China
Scientific Tracks Abstracts: J Pharma Care Health Sys
TNF-related apoptosis-inducing ligand (TRAIL), a member of TNF superfamily, specifically induces apoptosis of tumor cells. It is cytotoxic to death receptor-expressing tumor cells in vitro at the low concentration of nanomole. However, owing to the short serum half-life, TRAIL exerts poor in vivo antitumor effect in the preclinical test as well as in clinical trials. IgG is one type of long-acting proteins in plasma. IgG-binding might prolong the serum half-life thus enhance the in vivo antitumor effect of TRAIL. To endow the IgG-binding ability to TRAIL, a IgG-binding domain (IgBD) was genetically fused to the N-terminus of TRAIL. The fusion protein IgBD-TRAIL was similar to TRAIL in cytotoxicity. IgBD-TRAIL could bind both human IgG and mouse IgG and IgG-binding did not reduce its cytotoxicity. The serum half-life of IgBD-TRAIL in mice was 50-60 times longer than that of TRAIL and the tumor uptake of IgBD-TRAIL was 4-7 times more than that of TRAIL. In the treatment of mice bearing COLO 205 tumor grafts with average tumor volume of 150 mm3, a single dose of intravenously injected IgBD-TRAIL (5mg/kg) eradicated all tumor grafts within one week. However, the same amount of TRAIL only suppressed the tumor growth. Moreover, in mice bearing HCT116 or LS174T tumor grafts, intravenous injection of a single dose (5mg/kg) of IgBD-TRAIL definitely suppressed the tumor growth. But TRAIL showed a little antitumor effect in these mice, demonstrating that intravenously injected IgBD-TRAIL exerted greater antitumor effect than TRAIL. These results indicated that binding to endogenous IgG could prolong the half-life thus enhance the antitumor effect of TRAIL. IgBD-mediated IgG binding might be a novel approach for drug delivery.
Feng Yanru is a PhD student of Sichuan University, China. His expertise is focused on Immune modulatory engineering proteins. He has done his Bachelor’s degree in Southwest University and his research Focus on Plant Protection
E-mail: 359121844@qq.com