Status quo in antibody-drug conjugates-can glyco-enzymes solve the current challenges?

Over the last years,a novel class of anti-cancer drugs named antibody-drug conjugates (adcs) has been developed. due to their limited off-target toxicity but highly potent cytotoxicity at tumor sites,adcs have proven to be a good alternative to ordinary cancer treatment,such as chemotherapy or combination therapy. numerous enhancements in antibody-drug engineering led to highly potent tumor targeting drugs with a wide therapeutic window. two adcs (brentuximab vedotin and trastuzumab emtansine) are already on the market and many others are in clinical trials. however,unstable linkers,low drug potency and unwanted bystander-effects are only some of the drawbacks of adcs. enzymes used in combination with prodrugs happen to be a promising alternative. the glyco-enzyme horseradish peroxidase (hrp) has proven to activate the hormone indole-3-acetic acid (iaa) to a highly potent cytotoxic drug. this combination of iaa and hrp has been investigated for the use in strategies such as gene-directed enzyme prodrug therapy (gdept) and antibody-directed enzyme prodrug therapy (adept). this article reviews the current state of research in adc engineering and describes the potential major enhancements through use of glycoenzymes in combination with a prodrug. © 2017 bentham science publishers.