title: Evaluation of a panel of human monoclonal antibodies to D and exploration of the synergistic effects of blending IgG1 and IgG3 antibodies on their in vitro biologic function.
abstract: BACKGROUND
  The D immunoprophylaxis program has successfully reduced the incidence of Rh hemolytic disease of the newborn (HDN), but it has also reduced the availability of plasma-derived polyclonal anti-D, which constitutes the current therapeutic product. Human monoclonal anti-D from hybridoma cell lines may be an acceptable alternative, and clinical efficacy of each anti-D is being evaluated in several centers.
  
  
  METHODS
  This study represents the largest assessment (outside of the International Workshops) of human D monoclonal antibodies for potential therapeutic use. The in vitro biologic activity and immunologic and serologic reactivity of a coded panel of 20 D antibodies (THERAD) was investigated. The bioassays used were lymphocyte (K-cell) antibody-dependent cell-mediated cytotoxicity (ADCC), monocyte ADCC, and monocyte chemiluminescence, which together reflect the processes involved in antibody-coated red cell destruction in vivo. From this panel, six antibodies (THERADs 14, 19, 22, 23, 27, and 28, comprising 3 IgG1 and 3 IgG3 D monoclonal antibodies) were further selected to investigate the effects of blending in the three bioassays.
  
  
  RESULTS
  Several THERAD blends displayed greater activity than their component parts, in the range of 6 to 124 percent. There was no evidence to suggest functional blocking effects with this restricted panel of antibodies.
  
  
  CONCLUSIONS
  The THERAD blends containing both IgG1 and IgG3 anti-D appeared to be the most functionally active, as did blends containing antibodies to two distinct D epitopes. This in vitro evidence has important implications for the future formulation of an effective monoclonal preparation for the prevention of Rh HDN.
authors.affiliation: Department of Medicine & Therapeutics, University of Aberdeen, Scotland. sylvia.armstrong@snbts.csa.scot.nhs.uk
authors.forename: S S
authors.initials: SS
authors.lastname: Armstrong-Fisher
authors.forename: M C
authors.initials: MC
authors.lastname: Carter
authors.forename: I
authors.initials: I
authors.lastname: Downing
authors.forename: R H
authors.initials: RH
authors.lastname: Fraser
authors.forename: G E
authors.initials: GE
authors.lastname: Inglis
authors.forename: E K
authors.initials: EK
authors.lastname: Allan
authors.forename: A
authors.initials: A
authors.lastname: Mackie
authors.forename: C V
authors.initials: CV
authors.lastname: Prowse
authors.forename: J G
authors.initials: JG
authors.lastname: Templeton
authors.forename: S J
authors.initials: SJ
authors.lastname: Thorpe
authors.forename: S J
authors.initials: SJ
authors.lastname: Urbaniak
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D004357:Drug Synergism; D000939:Epitopes / Q000276:immunology; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D011247:Pregnancy; D012203:Rh Isoimmunization / Q000517:prevention & control*; D012204:Rh-Hr Blood-Group System / Q000276:immunology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000939:Epitopes; D007074:Immunoglobulin G; D007519:Isoantigens; D012204:Rh-Hr Blood-Group System; C048844:anti-IgG