Harnessing the immune system via FcγR function in immune therapy: A pathway to next‐gen mAbs

作者: Alicia M Chenoweth , Bruce D Wines , Jessica C Anania , P Mark Hogarth

DOI: 10.1111/IMCB.12326

关键词:

摘要: The human fragment crystallizable (Fc)γ receptor (R) interacts with antigen-complexed immunoglobulin (Ig)G ligands to both activate and modulate a powerful network of inflammatory host-protective effector functions that are key the normal physiology immune resistance pathogens. More than 100 therapeutic monoclonal antibodies (mAbs) approved or in late stage clinical trials, many which harness potent FcγR-mediated systems varying degrees. This is most evident for targeting cancer cells inducing antibody-dependent killing phagocytosis but also true some degree mAbs neutralize remove small macromolecules such as cytokines other Igs. use mAb therapeutics has revealed "scaffolding" role FcγR which, different contexts, may either underpin action agonism trigger catastrophic adverse effects. still unmet need cancers, diseases emerging infections severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires increased effort on development improved novel mAbs. A more mature appreciation immunobiology individual function complexity relationships between FcγRs fueling efforts develop "next-gen" antibodies. Such strategies now include focused glycan protein engineering Fc increase affinity and/or tailor specificity selective engagement activating inhibitory FcγRIIb alternatively, ablation interaction altogether. review touches recent aspects IgG its relationship present future actions

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