title: CCL20 neutralization by a monoclonal antibody in healthy subjects selectively inhibits recruitment of CCR6+cells in an experimental suction blister.
abstract: OBJECTIVE
  GSK3050002, a humanized IgG1κ antibody with high binding affinity to human CCL20, was administered in a first-in-human study to evaluate safety, pharmacokinetics (PK) and pharmacodynamics (PD). An experimental skin suction blister model was employed to assess target engagement and the ability of the compound to inhibit recruitment of inflammatory CCR6 expressing cells.
  
  
  METHODS
  This study was a randomized, double-blind (sponsor open), placebo-controlled, single-centre, single ascending intravenous dose escalation trial in 48 healthy male volunteers.
  
  
  RESULTS
  GSK3050002 (0.1-20 mg kg-1) was well tolerated and no safety concerns were identified. The PK was linear over the dose range, with a half-life of approximately 2 weeks. Complex of GSK3050002/CCL20 increased in serum and blister fluid with increasing doses of GSK3050002. There were dose-dependent decreases in CCR6+cell recruitment to skin blisters with maximal effects at doses of 5 mg kg-1and higher, doses at which GSK3050002/CCL20 complex in serum and blister fluid also appeared to reach maximum levels.
  
  
  CONCLUSIONS
  These results indicate a relationship between PK, target engagement and PD, suggesting a selective inhibition of recruitment of CCR6+cells by GSK3050002 and support further development of GSK3050002 in autoimmune and inflammatory diseases.
authors.affiliation: GlaxoSmithKline, Hertfordshire, UK.
authors.forename: Gerben
authors.identifier: http://orcid.org/0000-0002-1465-9178
authors.initials: G
authors.lastname: Bouma
authors.affiliation: GlaxoSmithKline, Hertfordshire, UK.
authors.forename: Stefano
authors.initials: S
authors.lastname: Zamuner
authors.affiliation: GlaxoSmithKline, Hertfordshire, UK.
authors.forename: Kirsty
authors.initials: K
authors.lastname: Hicks
authors.affiliation: GSK Clinical Unit, Cambridge, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Want
authors.affiliation: GSK Clinical Unit, Cambridge, UK.
authors.forename: João
authors.initials: J
authors.lastname: Oliveira
authors.affiliation: GlaxoSmithKline, Hertfordshire, UK.
authors.forename: Arpita
authors.initials: A
authors.lastname: Choudhury
authors.affiliation: GlaxoSmithKline, Hertfordshire, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Brett
authors.affiliation: GlaxoSmithKline, Hertfordshire, UK.|MedImmune, Cambridge, UK.
authors.forename: Darren
authors.initials: D
authors.lastname: Robertson
authors.affiliation: GlaxoSmithKline, Hertfordshire, UK.
authors.forename: Leigh
authors.initials: L
authors.lastname: Felton
authors.affiliation: GlaxoSmithKline, Hertfordshire, UK.|GN Clinical Consulting Ltd, London, UK.
authors.forename: Virginia
authors.initials: V
authors.lastname: Norris
authors.affiliation: GSK Clinical Unit, Cambridge, UK.
authors.forename: Disala
authors.initials: D
authors.lastname: Fernando
authors.affiliation: GlaxoSmithKline, Hertfordshire, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Herdman
authors.affiliation: GlaxoSmithKline, Hertfordshire, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Tarzi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology*; D001768:Blister / Q000276:immunology* / Q000378:metabolism; D002452:Cell Count; D054418:Chemokine CCL20 / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D054399:Receptors, CCR6 / Q000276:immunology*; D013396:Suction / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D054399:Receptors, CCR6; C000626978:GSK3050002
keywords: CCL20; CCR6; Th17; chemotaxis