Antibody Engineering - Tailor-Made Next Generation Antibodies by Molecular Design

The implementation of therapeutic antibodies has revolutionized the therapy of cancer patients. Based on the clinical success of prototypic tumor-targeting antibodies like rituximab and trastuzumab, the way for a variety of next-generation antibodies with improved characteristics was opened. Innovations in techniques to generate humanized or even human molecules (e.g. phage display, mice engineered to express human antibody repertoires) were key for the clinical triumph of first-generation antibodies. Despite the proven clinical activity in different cancer entities, not all patients respond to antibody therapy. Consequently, novel approaches to improve this generally well tolerated therapy are major areas of research in academia and in pharmaceutical industry. A deeper understanding of pathophysiological coherences, identification of critical checkpoints in the interaction of tumor cells and the immune system as well as novel insights into the mechanisms of action mediated by therapeutic antibodies have fueled innovations in antibody engineering. Obvious engineering strategies include approaches in improving IgG intrinsic effector mechanisms such as antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), or complement-dependent cytotoxicity (CDC). Besides engineering conventional IgG antibodies, innovative antibody derivatives such as bispecific antibodies, antibody drug conjugates, and antibody fusion proteins have been developed and corresponding prototypic agents were recently approved or are in various phases of clinical development. Several aspects of established and emerging antibody engineering technologies are addressed in this issue of Transfusion Medicine and Hemotherapy (fig. (fig.11)