title: Antibody-dependent cell cytotoxicity: immunotherapy strategies enhancing effector NK cells.
abstract: Antibody-dependent cellular cytotoxicity (ADCC) is a set of mechanisms that target cells coated with IgG antibodies of the proper subclasses (IgG1 in the human) to be the prey of cell-to-cell cytolysis executed by immune cells expressing FcRIIIA (CD16A). These effectors include not only natural killer (NK) cells but also other CD16+subsets such as monocyte/macrophages, NKT cells or γδ T cells. In cancer therapy, ADCC is exploited by antibodies that selectively recognize proteins on the surface of malignant cells. An approach to enhance antitumor activity is to act on effector cells so they are increased in their numbers or enhanced in their individual (on a cell per cell basis) ADCC performance. This enhancement can be therapeutically attained by cytokines (that is, interleukin (IL)-15, IL-21, IL-18, IL-2); immunostimulatory monoclonal antibodies (that is, anti-CD137, anti-CD96, anti-TIGIT, anti-KIR, anti-PD-1); TLR agonists or by adoptive infusions of ex vivo expanded NK cells which can be genetically engineered to become more efficient effectors. In conjunction with approaches optimizing IgG1 Fc affinity to CD16, acting on effector cells offers hope to achieve synergistic immunotherapy strategies.
authors.affiliation: Program of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), Pamplona, Spain.|Navarra Institute for Health Research (IDISNA), Pamplona, Spain.
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Ochoa
authors.affiliation: Program of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), Pamplona, Spain.|Navarra Institute for Health Research (IDISNA), Pamplona, Spain.
authors.forename: Luna
authors.initials: L
authors.lastname: Minute
authors.affiliation: Program of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), Pamplona, Spain.|Navarra Institute for Health Research (IDISNA), Pamplona, Spain.|Servicio de Inmunología e Inmunoterapia, Clínica Universidad de Navarra, Pamplona, Spain.|Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Rodriguez
authors.affiliation: Program of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), Pamplona, Spain.|Navarra Institute for Health Research (IDISNA), Pamplona, Spain.
authors.forename: Saray
authors.initials: S
authors.lastname: Garasa
authors.affiliation: Department of Medical Oncology (REDISSEC), Hospital Costa del Sol, Marbella, Spain.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Perez-Ruiz
authors.affiliation: Program of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), Pamplona, Spain.|Servicio de Inmunología e Inmunoterapia, Clínica Universidad de Navarra, Pamplona, Spain.|Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Inogés
authors.affiliation: Program of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), Pamplona, Spain.|Navarra Institute for Health Research (IDISNA), Pamplona, Spain.|Servicio de Inmunología e Inmunoterapia, Clínica Universidad de Navarra, Pamplona, Spain.|Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Melero
authors.affiliation: Program of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), Pamplona, Spain.|Navarra Institute for Health Research (IDISNA), Pamplona, Spain.|Servicio de Inmunología e Inmunoterapia, Clínica Universidad de Navarra, Pamplona, Spain.|Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Berraondo
mesh_terms: D000818:Animals; D000915:Antibody Affinity; D000920:Antibody-Dependent Cell Cytotoxicity; D000951:Antigens, Neoplasm / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation; D008264:Macrophages / Q000502:physiology*; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D016207:Cytokines; C496124:FCGR3A protein, human; D016692:Receptors, Antigen, T-Cell, gamma-delta; D017452:Receptors, IgG; D051193:Toll-Like Receptors