Immunoglobulin isotype knowledge and application to Fc engineering

Monoclonal antibody-based drugs continue to be one of the most rapidly growing classes of therapeutic molecules. At present, the majority of approved therapeutic antibodies are of the human IgG1 format, which can elicit immune effector functions (e.g., antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement-dependent cytotoxicity). However, there is a wealth of functional diversity that is present in other isotypes and IgG subclasses that can be exploited to improve clinical safety and performance by increasing stability, reduction of adverse events, modulation of effector functions, and by the engagement of two antigens by a single antibody. This review presents an overview of the different antibody isotypes and subclasses and details how exchanging amino acids between different isotypes (i.e., 'cross-isotypes') can be exploited to generate novel therapeutic platforms.