Monoclonal antibodies - A repertoire of therapeutics

Antibodies are a class of biomolecules armed with extraordinary diversity, unmatched in the biological world by any other class of molecules. This characteristic feature equips antibodies to recognize, bind, and eliminate an infinite number of pathogens/antigens facilitated by their effector functions. The repertoire of natural binding specificities of antibodies (Abs) is greater than the calculated estimate of ∼10¹² in humans, as a naive, single antigen-binding site may bind more than one antigen employing the plasticity in antigen-antibody interactions, potentiating Abs to fight infinite pathogenic insults and restrict the development of cancers. Additionally, advanced technological interventions, by allowing manipulation of the germline and acquired specificities of human/animal immunoglobulins (Ig) have contributed immensely to broaden their existing repertoire and scope of clinical applications. The available natural repertoire of Ig and Ig-like molecules in other animals, e.g., mice, horses, cows, pigs, rabbits, camels, llamas, etc., further diversified the source of unique antigen-binding specificities. The recombinant DNA technology, in association with hybridoma , transgenic, and phage display technologies, has helped create a parallel repertoire of unique antibody molecules [animal Abs, camelid heavy chain Abs (hcAbs), chimeric Abs, chimeric hcAbs, humanized Abs, humanized nanobody (Nb)-hcAbs, human Abs, etc.], monoclonal Ab (mAb) derived fragments [antigen-binding-fragment (Fab), single-chain-variable-fragment (scFv), variable-fragement (Fv), single-variable-domain of hcAbs (V_HH), bispecific scFv, diabodies, triabodies, intrabodies, bispecific Fabs, tri-specific Fabs, etc.), and immunoconjugates generated by fusing/conjugating mAb fragments with enzyme, toxin, prodrug etc., molecules. The current chapter provides a detailed description of the natural and engineered antibody repertoires and discusses various strategies using which these molecules are being inducted as novel immunotherapeutics for treating a significant number of human diseases.