title: Manufacturing Natural Killer Cells as Medicinal Products.
abstract: Natural Killer (NK) cells are innate lymphoid cells (ILC) with cytotoxic and regulatory properties. Their functions are tightly regulated by an array of inhibitory and activating receptors, and their mechanisms of activation strongly differ from antigen recognition in the context of human leukocyte antigen presentation as needed for T-cell activation. NK cells thus offer unique opportunities for new and improved therapeutic manipulation, eitherin vivoorin vitro, in a variety of human diseases, including cancers. NK cell activity can possibly be modulatedin vivothrough direct or indirect actions exerted by small molecules or monoclonal antibodies. NK cells can also be adoptively transferred following more or less substantial modifications through cell and gene manufacturing, in order to empower them with new or improved functions and ensure their controlled persistence and activity in the recipient. In the present review, we will focus on the technological and regulatory challenges of NK cell manufacturing and discuss conditions in which these innovative cellular therapies can be brought to the clinic.
authors.affiliation: CBT-1409: INSERM, Aix Marseille Univ, Institut Paoli-Calmettes, AP-HM, Marseille, France; CRCM: INSERM, CNRS, Aix Marseille Univ, Institut Paoli-Calmettes, CRCM, Marseille, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Chabannon
authors.affiliation: CBT-1409: INSERM, Aix Marseille Univ, Institut Paoli-Calmettes, AP-HM, Marseille, France; CRCM: INSERM, CNRS, Aix Marseille Univ, Institut Paoli-Calmettes, CRCM, Marseille, France.
authors.forename: Bechara
authors.initials: B
authors.lastname: Mfarrej
authors.affiliation: UM2, INSERM, Centre d'Immunologie de Marseille-Luminy, U1104, CNRS UMR7280, Aix-Marseille University , Marseille , France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Guia
authors.affiliation: UM2, INSERM, Centre d'Immunologie de Marseille-Luminy, U1104, CNRS UMR7280, Aix-Marseille University , Marseille , France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Ugolini
authors.affiliation: CRCM: INSERM, CNRS, Aix Marseille Univ, Institut Paoli-Calmettes, CRCM , Marseille , France.
authors.forename: Raynier
authors.initials: R
authors.lastname: Devillier
authors.affiliation: CRCM: INSERM, CNRS, Aix Marseille Univ, Institut Paoli-Calmettes, CRCM , Marseille , France.
authors.forename: Didier
authors.initials: D
authors.lastname: Blaise
authors.affiliation: UM2, INSERM, Centre d'Immunologie de Marseille-Luminy, U1104, CNRS UMR7280, Aix-Marseille University, Marseille, France; Laboratoire d'Immunologie, Hôpital de la Conception, Assistance Publique - Hôpitaux de Marseille, Aix-Marseille University, Marseille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.affiliation: CBT-1409: INSERM, Aix Marseille Univ, Institut Paoli-Calmettes, AP-HM, Marseille, France; CRCM: INSERM, CNRS, Aix Marseille Univ, Institut Paoli-Calmettes, CRCM, Marseille, France.
authors.forename: Boris
authors.initials: B
authors.lastname: Calmels
keywords: cell transplant; cellular therapy; immuno-oncology; immunotherapy; innate lymphoid cells; manufacturing; natural killer cells