Antibody –drug conjugates (ADCs) for cancer therapy: Strategies, challenges, and successes

Third ‐generation antibody–drug conjugates are more effective, showing lower levels of unconjugated monoclonal antibodies, more‐stable linkers, improved pharmacokinetic properties, and safety profiles. AbstractTargeted delivery of therapeutic molecules into cancer cells is considered as a promising strategy to tackle cancer. Antibody –drug conjugates (ADCs), in which a monoclonal antibody (mAb) is conjugated to biologically active drugs through chemical linkers, have emerged as a promising class of anticancer treatment agents, being one of the fastest growing fields in cancer therapy. The failure of early ADCs led researchers to explore strategies to develop more effective and improved ADCs with lower levels of unconjugated mAbs and more‐stable linkers between the drug and the antibody, which show improved pharmacokinetic properties, therapeutic indexes, and safety profiles. Such improvements resulted in the US Food an d Drug Administration approvals of brentuximab vedotin, trastuzumab emtansine, and, more recently, inotuzumab ozogamicin. In addition, recent clinical outcomes have sparked additional interest, which leads to the dramatically increased number of ADCs in clinical development. The present review explo res ADCs, their main characteristics, and new research developments, as well as discusses strategies for the selection of the most appropriate target antigens, mAbs, cytotoxic drugs, linkers, and conjugation chemistries.

Source: Journal of Cellular Physiology - November 27, 2018 Category: Cytology Authors: Meghdad Abdollahpour ‐Alitappeh, Majid Lotfinia, Tohid Gharibi, Jalal Mardaneh, Behrouz Farhadihosseinabadi, Pegah Larki, Babak Faghfourian, Koushan Sineh Sepehr, Kazem Abbaszadeh‐Goudarzi, Ghasem Abbaszadeh‐Goudarzi, Behrooz Johari, Moha Tags: REVIEW ARTICLE Source Type: research