title: B-cell targeted therapeutics in clinical development.
abstract: B lymphocytes are the source of humoral immunity and are thus a critical component of the adaptive immune system. However, B cells can also be pathogenic and the origin of disease. Deregulated B-cell function has been implicated in several autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. B cells contribute to pathological immune responses through the secretion of cytokines, costimulation of T cells, antigen presentation, and the production of autoantibodies. DNA-and RNA-containing immune complexes can also induce the production of type I interferons, which further promotes the inflammatory response. B-cell depletion with the CD20 antibody rituximab has provided clinical proof of concept that targeting B cells and the humoral response can result in significant benefit to patients. Consequently, the interest in B-cell targeted therapies has greatly increased in recent years and a number of new biologics exploiting various mechanisms are now in clinical development. This review provides an overview on current developments in the area of B-cell targeted therapies by describing molecules and subpopulations that currently offer themselves as therapeutic targets, the different strategies to target B cells currently under investigation as well as an update on the status of novel therapeutics in clinical development. Emerging data from clinical trials are providing critical insight regarding the role of B cells and autoantibodies in various autoimmune conditions and will guide the development of more efficacious therapeutics and better patient selection.
authors.affiliation: MedImmune, LLC, Department of Research, One MedImmune Way, Gaithersburg, MD 20854, USA.
authors.forename: Stephan
authors.initials: S
authors.lastname: Blüml
authors.forename: Kathleen
authors.initials: K
authors.lastname: McKeever
authors.forename: Rachel
authors.initials: R
authors.lastname: Ettinger
authors.forename: Josef
authors.initials: J
authors.lastname: Smolen
authors.forename: Ronald
authors.initials: R
authors.lastname: Herbst
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors* / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D018579:Patient Selection; D000069283:Rituximab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D053264:B-Cell Activating Factor; D007155:Immunologic Factors; D000069283:Rituximab; C511911:belimumab; C575974:tabalumab