title: Saturation monitoring of VX15/2503, a novel semaphorin 4D-specific antibody, in clinical trials.
abstract: BACKGROUND
  Receptor occupancy, or saturation, assays are often utilized in preclinical and clinical development programs to evaluate the binding of a biologic to a cellular target. These assays provide critical information regarding the dose of drug required to "saturate" the target as well as important pharmacodymamic (PD) data. A flow cytometric method was developed to measure the degree of Semaphorin 4D (SEMA4D; CD100) saturation by VX15/2303, an investigational monoclonal antibody specific for SEMA4D.
  
  
  METHODS
  The assay detects VX15/2503, a human IgG4 specific for SEMA4D, with an IgG4 -specific monoclonal antibody.
  
  
  RESULTS
  Data generated allowed assessment of two related SEMA4D-specific pharmacodynamic (PD) markers: (1) The measurement of cellular SEMA4D (cSEMA4D) saturation by VX15/2503, and (2) the cell membrane expression levels of cSEMA4D.
  
  
  CONCLUSIONS
  This assay specifically and reproducibly measured cSEMA4D saturation and expression levels. Evaluation of the SEMA4D-specific PD markers were critical in determining the clinical saturation threshold of cSEMA4D by VX15/2503.
authors.affiliation: Vaccinex Inc, Rochester, New York.
authors.forename: Terrence L
authors.initials: TL
authors.lastname: Fisher
authors.affiliation: Vaccinex Inc, Rochester, New York.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Seils
authors.affiliation: Vaccinex Inc, Rochester, New York.
authors.forename: Christine
authors.initials: C
authors.lastname: Reilly
authors.affiliation: Covance Central Laboratory Services, Indianapolis, Indiana.
authors.forename: Virginia
authors.initials: V
authors.lastname: Litwin
authors.affiliation: Covance Central Laboratory Services, Indianapolis, Indiana.
authors.forename: Lisa
authors.initials: L
authors.lastname: Green
authors.affiliation: Covance Central Laboratory Services, Indianapolis, Indiana.
authors.forename: Janelle
authors.initials: J
authors.lastname: Salkowitz-Bokal
authors.affiliation: Covance Central Laboratory Services, Indianapolis, Indiana.
authors.forename: Robin
authors.initials: R
authors.lastname: Walsh
authors.affiliation: Covance Central Laboratory Services, Indianapolis, Indiana.
authors.forename: Sarah
authors.initials: S
authors.lastname: Harville
authors.affiliation: Vaccinex Inc, Rochester, New York.
authors.forename: John E
authors.initials: JE
authors.lastname: Leonard
authors.affiliation: Vaccinex Inc, Rochester, New York.
authors.forename: Ernest
authors.initials: E
authors.lastname: Smith
authors.affiliation: Vaccinex Inc, Rochester, New York.
authors.forename: Maurice
authors.initials: M
authors.lastname: Zauderer
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D015703:Antigens, CD / Q000097:blood / Q000276:immunology / Q000302:isolation & purification*; D005434:Flow Cytometry; D064368:Healthy Volunteers; D006801:Humans; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D039961:Semaphorins / Q000097:blood / Q000276:immunology / Q000302:isolation & purification* / Q000493:pharmacokinetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; C093224:CD100 antigen; D039961:Semaphorins; C000604277:VX15-2503 monoclonal antibody
keywords: Semaphorin4D; VX15/2503; clinical trials; receptor-occupancy; saturation