LAUSR

Therapeutic antibodies represent one of the most significant advances in the history of medicine. Progress in the antibody therapy field was initially slow and intermittent. The first therapeutic antibody, murine-derived Murononab OKT3 for acute organ rejection, was approved by the FDA in 1986, more than a decade after the discovery of the hybridoma technology by Milstein and Köhler in 1975 (Kohler and Milstein, 1975; Emmons and Hunsicker, 1987). As a result of technological breakthroughs starting in the 1980s, progress in therapeutic antibodies accelerated dramatically. During the last 30 years, antibodies have become a major drug modality for cancer, autoimmune, infectious, cardiovascular, neurological, and other diseases. The rapid rise of antibodybased therapies is largely due to their desirable safety profile, target specificity, and efficacy. As a practitioner in the field and like many others, I have stopped from time to time to take the pulse of the therapeutic antibody landscape (An, 2009, 2010). This special issue provides readers with a snapshot of the current state of therapeutic antibodies. We begin with a comprehensive and expert review on current progress in innovative engineered antibodies by Strohl (2017). Some astonishing statistics were referenced in the review. For instance, more than 74 antibody-based molecules are currently in clinical use and at least 645 antibody based therapies are in different stages of clinical trials. Antibody therapies come in different forms and sizes, such as naked IgGs, antibody drug conjugates (ADCs), bispecific antibodies, Fc fusion proteins, radioimmunoglobulins, and antibody fragments. In addition to the classical targeted therapies such as the HER2 targeting trastuzumab for breast cancer treatment, clinical application of antibody therapies is constantly expanding. Now there are antibodies targeting T cell checkpoints, T-cell redirected bispecific antibodies, and chimeric antigen receptor (CAR) cell-based candidates. Researchers are making progress in new clinical indications and novel disease targets. Further, significant progress is continuously being made on many technology fronts, including new routes of delivery: proteins across the blood-brain barrier; oral delivery to the gut; delivery to the cellular cytosol; and geneand viral-based delivery of antibodies. One advantage of antibody based therapies is the long half-life of the molecule. Many factors can influence the pharmacokinetics (PK) of a mAb or Fc-fusion molecule, with the primary determinant being FcRn-mediated recycling. In an expert review on antibody PK, Liu discusses the latest development in enhancing half-life through antibody engineering. He describes the impact of glycosylation, target mediated drug disposition (TMDD), anti-drug antibody (ADA), route of administration, and formulation on antibody PK (Liu, 2017). Glycosylation plays an important role in the biological activities of antibodies. Manipulation of the glycosylation pattern of an antibody has been used to improve the pharmaceutical properties of the molecule. Mimura et al. summarized the status of applying glycoengineering to improve the safety, functionality, and efficacy of therapeutic antibodies in the era of precision medicine (Mimura et al., 2017). The antibody-drug conjugate (ADC), an antibody conjugated with potent cytotoxic small molecules through chemical linkers, is an emerging therapeutic format that has great potential to make a paradigm shift in cancer chemotherapy. Tsuchikama and An present an update on the current status in conjugation and linker chemistry design and strategies to develop clinically effective ADCs from medicinal chemistry and pharmacology standpoints (Tsuchikama and An, 2016). In the oncology area, some of the most exciting new approaches involve antibody modulation of T-cells. Tan et al.