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.
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.
Armstrong-Fisher
S S
SS
Department of Medicine & Therapeutics, University of Aberdeen, Scotland. sylvia.armstrong@snbts.csa.scot.nhs.uk
Carter
M C
MC
Downing
I
I
Fraser
R H
RH
Inglis
G E
GE
Allan
E K
EK
Mackie
A
A
Prowse
C V
CV
Templeton
J G
JG
Thorpe
S J
SJ
Urbaniak
S J
SJ
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*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000939:Epitopes; D007074:Immunoglobulin G; D007519:Isoantigens; D012204:Rh-Hr Blood-Group System; C048844:anti-IgG