4^th European Biopharma Congress

TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF cytokine family capable of inducing apoptosis by

its cognate receptors in cancer cells without apparent toxicity to normal cells. TRAIL has been considered as an anticancer

drug due to its unique ability to selectively induce DR-mediated apoptosis in transformed cells. To date, recombinant human

TRAIL and antibodies directed against TRAIL-R1 or TRAIL-R2 have been tested clinically. However, these have been

disappointing, showing a very limited benefit as an antitumor agent basically due to their poor agonistic activity of these

agents. And in recent years, the physiological importance of TRAIL has expanded beyond being a tumoricidal molecule to

one critical for a number of clinical settings - ranging from fibrosis and autoimmunity to cardiovascular anomalies. In an

attempt to overcome the poor agonistic activity and also low stability and solubility of rTRAIL in vivo, we developed a delivery

system by using PEGylation. PEGylation of protein improves solubility, reduces the interaction with blood cells and serum

proteins, provides a better biocompatibility, and extends circulation times. We recently confirmed the therapeutic efficacy of

this prolonged systemic TRAIL in vivo on different animal models. In this talk, I will introduce how our research experience,

at the crossroads of bioconjugation, drug delivery, and biology, enabled the engineering of stable TRAIL-based therapies,

the discovery of clinically viable targets for cancer, inflammatory, fibrosis and autoimmune disease therapy towards clinical

translation.