Elucidation of the Molecular Mechanism Underlying Function of Therapeutic Antibodies and the Development of Quality Assessment Methods

In recent years, therapeutic antibodies with various molecular modifications, such as antibody–drug conjugates, glycoengineered antibodies, and bispecific antibodies, have been developed to address unmet medical needs, resulting in increasingly complex and diverse molecular characteristics. Antibody therapeutics are multifunctional molecules capable of binding not only target antigens but also to Fcγ receptors (FcγRs) and complement. To ensure their proper effector functions, exemplified by antibody-dependent cell-mediated cytotoxicity (ADCC), it is essential to identify and appropriately control their quality attributes that influence the effector functions. To date, we have conducted studies on (1) development of novel analytical methods utilizing antibody–FcγR binding affinity, (2) control of characteristics of antibody molecules through peptide conjugation, and (3) establishment of methods for evaluating the higher-order structure of antibodies using spectroscopic and statistical approaches. The molecular mechanism underlying the effector function of therapeutic antibodies and the advanced quality assessment methods developed in this study are expected to contribute to the promotion of development and quality assurance of next-generation therapeutic antibodies that continue to evolve through diverse molecular modifications.