title: In vitro cytokine release assays: reducing the risk of adverse events in man.
abstract: The induction of cytokine release is a common consequence of the administration of therapeutic antibodies and in most cases is either tolerated by the patient or can be managed clinically by the administration of corticosteroids. However, in 2006, the administration of TGN1412 to six patients in a Phase I trial resulted in a unprecedentedly high level of cytokine release, systemic organ failure and the hospitalization of the subjects. Whilst the path to failure in this incident was multifactorial, at least one contributing factor was the lack of a robust in vitro model that would allow the prediction of the in vivo activity of a therapeutic antibody. In this article we review the current 'state of the art' of in vitro cytokine release assays and explore potential future developments.
authors.affiliation: Huntingdon Life Sciences, Alconbury, Cambridgeshire, PE28 4HS, UK. kirtonc@ukorg.huntingdon.com
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Kirton
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Gliddon
authors.forename: Gregory
authors.initials: G
authors.lastname: Bannish
authors.forename: Gary P
authors.initials: GP
authors.lastname: Bembridge
authors.forename: Lee A
authors.initials: LA
authors.lastname: Coney
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D016207:Cytokines / Q000032:analysis* / Q000378:metabolism*; D006801:Humans
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; C509303:TGN-1412