title: The coming of age of engineered multivalent antibodies.
abstract: The development of monoclonal antibody (mAb) technology has had a profound impact on medicine. The therapeutic use of first-generation mAb achieved considerable success in the treatment of major diseases, including cancer, inflammation, autoimmune, cardiovascular, and infectious diseases. Next-generation antibodies have been engineered to further increase potency, improve the safety profile and acquire non-natural properties, and constitute a thriving area of mAb research and development. Currently, a variety of alternative antibody formats with modified architectures have been generated and are moving fast into the clinic. In fact, the bispecific antibody blinatumomab was the first in its class to be approved by the US Food and Drug Administration (FDA) as recently as December 2014. Here, we outline the fundamental strategies used for designing the next generation of therapeutic antibodies, as well as the most relevant results obtained in preclinical studies and clinical trials.
authors.affiliation: Molecular Immunology Unit, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Nuñez-Prado
authors.affiliation: Molecular Immunology Unit, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Compte
authors.affiliation: Department of Engineering, Aarhus University, Aarhus, Denmark.
authors.forename: Seandean
authors.initials: S
authors.lastname: Harwood
authors.affiliation: FEBIO Research Group, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Álvarez-Méndez
authors.affiliation: Department of Clinical Medicine and Sino-Danish Center, Aarhus University, Aarhus, Denmark.
authors.forename: Simon
authors.initials: S
authors.lastname: Lykkemark
authors.affiliation: Molecular Immunology Unit, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain. Electronic address: lsalcober@salud.madrid.org.
authors.forename: Laura
authors.initials: L
authors.lastname: Sanz
authors.affiliation: Department of Engineering, Aarhus University, Aarhus, Denmark. Electronic address: lav@eng.au.dk.
authors.forename: Luis
authors.initials: L
authors.lastname: Álvarez-Vallina
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D000918:Antibody Specificity; D055808:Drug Discovery / Q000379:methods*; D000939:Epitopes; D006801:Humans; D011487:Protein Conformation; D015202:Protein Engineering / Q000379:methods*; D013329:Structure-Activity Relationship
chemical_list: D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D000939:Epitopes