Recombinant production and characterization of Par-4/SAC

Recombinant Par-4/SAC protein is capable of inducing apoptosis selectively in cancer cells without affecting the normal cells and, hence, has the potential to serve as a protein drug candidate for cancer treatment. Meanwhile, major challenges exist in the recombinant Par-4/SAC protein drug development, such as the low yield of recombinant protein production and the poor pharmacokinetic (PK) profile (with a short elimination half-life) of the protein. Nevertheless, encouraging progresses have been made during the last few years for improving both the yield of recombinant Par-4/SAC production and the PK profile. Particularly for improvement of the PK profile, the recently developed novel, long-lasting form of Par-4, known as <IndexTerm ID="ITerm1">Par-4Ex</IndexTerm>, is promising, because Par-4Ex has not only fully retained the unique <IndexTerm ID="ITerm2">anti-cancer activity</IndexTerm> of native Par-4, but also significantly prolonged the elimination half-life. As a result, Par-4Ex has a more potent in vivo anti-cancer activity compared to Par-4 itself. So, Par-4Ex may serve as a truly promising protein drug candidate for drug development moving forward. In addition, future effort to further prolong the elimination half-life may also include the structure-based rational design and testing of possible Par-4Ex mutants with improved binding affinity to neonatal Fc receptor (FcRn) in the acidic environment. In this way, the relatively longer elimination half-life of Par-4Ex may be extended further.