Preparation and characterization of a chimeric CD19 monoclonal antibody.
FMC63 is an IgG2a mouse monoclonal antibody belonging to the CD19 cluster. CD19 antibodies react with a 95kDa protein expressed by cells of the B lymphocyte lineage, from pre-B cells to mature B lymphocytes. CD19 antibodies have been suggested as candidates for immunological attack on leukaemic and lymphoma cells of the B lineage because the antigen is restricted to the B lineage. With the potential use of FMC63 in immunotherapy in mind, we have produced a mouse-human chimera in which the genes coding for the VDJ region of the heavy chain and the VJ region of the light chain derive from the FMC63 mouse hybridoma, while the C region genes code for human IgG1. The genes have been transfected back into a mouse myeloma line, which secretes low levels of immunoglobulin. (Ig). This Ig was purified and biotinylated in order to determine the specificity of the antibody. The chimeric antibody has a reaction profile concordant with the original FMC63 antibody, but has the properties of a human IgG1, including the ability to fix human complement. However, the antibody is not cytotoxic in vitro in the presence of complement or cells capable of mediating antibody-dependent cellular cytotoxicity. Possible reasons for this and ways of using the antibody are discussed.
Zola
H
H
Department of Clinical Immunology, Flinders Medical Centre, Bedford Park, South Australia.
MacArdle
P J
PJ
Bradford
T
T
Weedon
H
H
Yasui
H
H
Kurosawa
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000302:isolation & purification*; D000918:Antibody Specificity; D000920:Antibody-Dependent Cell Cytotoxicity; D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D001402:B-Lymphocytes / Q000276:immunology; D002678:Chimera; D003165:Complement System Proteins / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000302:isolation & purification; D051379:Mice; D015202:Protein Engineering
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D007074:Immunoglobulin G; D003165:Complement System Proteins