The main barriers of the preclinical and clinical application of TRAIL, tumor-necrosis-factor (TNF)-related apoptosis-inducing ligand, are poor pharmacokinetics and drug resistance in some tumor cell lines.
In order to break through the barriers, researchers found TRAIL114-281 (114 to 281 amino acids) with its half-life reveals no more than 30 minutes across species. Taking advantage of steric effects involved within TRAIL mutant conjugations, they conjugated maleimido activated PEG (polyethylene glycol) and MMAE (Monomethyl Auristatin E) with the mutated cysteines from different monomers of TRAIL successively, so the TRAIL trimer was modified for different purposes. The half-life of EG-TRAIL-vcMMAE conjugate received by the process was improved, with good in vivo targeting ability and antitumor activities. Apart from that, the conjugate a viable therapeutic and drug delivery strategy with no toxicity in xenograft models.