Stephen McCarthy

Background

About Stephen McCarthy

My research has helped to make potential therapeutic antibodies more efficacious, improve their drug safety profiles, and produce therapies that are more cost efficient for the patient. Now more than ever, it is a critical step in the process of research and development of a potential antibody-based therapeutic to consider the fragment crystallizable (Fc) domain, and what we want it to do when the molecule engages with it’s target antigen(s). Binding of the Fc domain to (and proper release from), the neonatal Fc receptor (FcRn) affects the serum half-life as well as the biodistribution of an antibody molecule. Binding to various Fc gamma receptors (FcγRs) on the surface of different immune cells helps to regulate cellular responses against the antigen-bearing target cell, e.g, ADCC via NK cells, phagocytosis by macrophages, as well as inhibition of immune responses. Multiplexed engagement with complement factor C1q initiates activation of the complement cascade for another route of cytotoxic destruction. Additionally, the options go beyond the choice of IgG subtype (subclass). IgA antibodies can activate the most abundant immune effector cell we have – neutrophils – through Fc engagement of the FcαR (CD89). My research has focused on the design and follow-up testing of novel antibody variants by making mutations within the receptor binding domains of the Fc to alter the properties of the antibody-mediated immune responses, as well as to allow for heterodimeric Fc formation to create bispecific antibodies, to provide longer (or shorter) serum half-life, and to confer stability to the antibody molecule in the presence of potentially destabilizing Fc mutations. My most recent publication describes three new Fc silenced variants and various analytical methods used to confirm silence. This manuscript, and others, are directly accessible on ResearchGate, the professional network for scientists, here: