Harnessing the immune system's arsenal: producing human monoclonal antibodies for therapeutics and investigating immune responses

Sullivan, Meghan; Kaur, Kaval; Pauli, Noel; Wilson, Patrick C.

Another attractive potential of monoclonal antibody treatment is the possibility of fine-tuning the function of an antibody by changing its "constant region." Our bodies naturally accomplish this using genetic recombination to pair the variable, antigen-binding exon with various specialized isotype gene exons (such as IgM, IgG1 through 4, IgA, and IgE). Antibodies vary in their effector functions depending on their isotype; isotypes confer the ability to lyse targets by activating lytic "complement" proteins in sera, and can cross mucosal barriers and bind specialized receptors on the surface of other immune cells, which can lead to antigen clearance or direct killing of the antibody-coated pathogen or protein. By outfitting the monoclonal antibody with the most appropriate effector function (or a cocktail thereof), we can take into account the desired outcome of a treatment, be it clearance of a pathogen or direct killing of cancerous cells. Such technological strides could make monoclonal antibodies a ubiquitous therapy for a variety of conditions and diseases.