The Best IgG Subclass for the Development of Therapeutic Monoclonal Antibody Drugs and their Commercial Production: A Review

Most of the clinically available monoclonal antibody (mAbs) drugs are Immunoglobulin G's (IgG's). The variability of the IgG subclasses is in the amino acid content of the hinge region which forms the basis of their stability and suitability for therapeutics development. Monoclonal antibody drug development is a tedious and long-term process requiring putting many factors into consideration. The variability in the stability, flexibility, mediation of antibody dependent cell cytotoxicity (ADCC), mediation of cellular dependent cytotoxicity (CDC), and C1q protein binding are major factors that determine the suitability of IgG subclasses for the development of therapeutics. It was reviewed that most of the marketed mAbs therapeutics are IgG1 subclass, this is due to its stability and less aggregate formation, triggering of effector function via the action of Fc domain binding to FcyRI, FcyRII, and FcyRIII, resulting to mediation of ADCC, CDC, and C1q cascade of signaling. However, IgG2 is also utilized for the development of therapeutic when neutralization of soluble antigen with reduce effector function is required, with some drugs in late stage development and also approved for commercial use. Also, IgG4 is utilized for the development of therapeutics drugs when the recruitment of the host effector function is not required. But IgG3 utilization for the development of therapeutics requires engineering of the amino acids content of the hinge region, without any commercially available drug that is IgG3. This review examines the suitable IgG subclasses with the capability of ADCC, CDC, and C1q mediation, and also provides future recommendation on the suitability of less stable IgG subclasses in the therapeutic development.