Article info 2015 3 (4)    003  (04)   pp.  154 ~ 161
Title Next generation antibody therapeutics: bispecific antibodies and antibody-drug conjugates
Authors Thi Thu Ha Nguyen1,+, Xuelian Bai1,+ and Hyunbo Shim1,2,*
Institutions 1Department of Life Science, Ewha Womans University, Seoul 03760, Korea, 2Department of Bioinspired Science, Ewha Womans University, Seoul 03760, Korea. *Correspondence: hshim@ewha.ac.kr. +Equal contribution.
Abstract A new generation of therapeutic antibody technologies has emerged last decade, most notable among which are bispecific antibodies and antibody-drug conjugates. Traditional monoclonal antibodies recognize a single target molecule and exert their therapeutic activity by neutralizing the target and/or through the effector functions. On the other hand, bispecific antibodies of various formats are able to bind two different targets simultaneously. Two major approaches to harness their bispecific binding activity for therapeutic application are being pursued: recruitment of immune effector cells to the diseased cells, and simultaneous/synergistic neutralization of two disease-causing molecules. Antibody-drug conjugates are disease-targeting monoclonal antibodies chemically conjugated to a highly cytotoxic compound. The internalization of the conjugate by endocytosis and subsequent release of the cytotoxin result in a potent and selective cytotoxic activity against cancerous target cells. Optimization of the drug, linker, and conjugation chemistry is a major technological challenge in developing antibody-drug conjugates. Despite their relatively recent emergence and technological difficulties, a few examples of these novel therapeutic modalities have been successfully developed and commercialized, and many others are in the late stages of clinical development. In this review, the background and the current status of technological development in this field is discussed, with emphasis on the detailed molecular design of these molecules.