title: In search of magic bullets: the golden age of immunotherapeutics.
abstract: Once upon a time, immunology was a black box, inflammatory and autoimmune diseases were a mystery, and relatively blunt tools were used to treat these diseases. In the last 40 years, advances in molecular biology, DNA recombination technology, and genome sequencing allowed immunologists to open the box. As the complexity and diversity of the immune response are unveiled, targeted cellular and molecular therapies now offer rational approaches to treat immune-mediated diseases. Here, we discuss how the tried and true bench-to-bedside strategies resulted in some spectacular successes, along with some puzzling failures. Conversely, the advent of targeted therapies in the clinic has led to a wealth of information that changes how we think about the pathogenesis of immune-mediated diseases and how we categorize disease. In turn, these insights can inform next-generation drug discovery and refine targeted therapies for the appropriate patient subsets.
authors.affiliation: Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA. Electronic address: osheajo@mail.nih.gov.
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Shea
authors.affiliation: Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kanno
authors.affiliation: Genentech Inc., One DNA Way, MS34, South San Francisco, CA 94080, USA. Electronic address: acc@gene.com.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Chan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy; D016207:Cytokines / Q000276:immunology / Q000627:therapeutic use; D055808:Drug Discovery; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D058990:Molecular Targeted Therapy
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines