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Pentamerisation of a scFv directed against TRAIL receptor 2 increases its antitumour efficacy
Author(s) -
Wang Wei,
He Wen,
Wang Lei,
Zhang Ge,
Gao Bin
Publication year - 2013
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2013.10
Subject(s) - avidity , pentamer , in vitro , in vivo , antibody , receptor , fusion protein , phage display , single chain variable fragment , chemistry , recombinant dna , cartilage oligomeric matrix protein , microbiology and biotechnology , monoclonal antibody , pharmacology , biology , immunology , medicine , biochemistry , osteoarthritis , alternative medicine , pathology , gene
Single‐chain variable fragments (scFvs) have been considered as promising therapeutic drugs. However, their low affinity and rapid clearance from the blood have limited their wider application clinically. In this study, we aimed to improve scFv antibodies by multimerising a scFv against the death receptor 5 (DR5, TNFR10B) through fusion with a coiled‐coil domain of human cartilage oligomeric matrix protein 48. By forming a pentamer, nick‐named a combody, the avidity of the scFv increased 10 4 ‐fold and combody was more effective than its monomeric counterpart for antitumour activity in both in vitro and in vivo experiments.