Expression of a functional mouse-human chimeric anti-CD19 antibody in the milk of transgenic mice.
Human B cell lymphomas are suitable targets for immunotherapy. Clinical trials with mouse-human chimeric B cell-specific monoclonal antibodies (mAbs) have already shown promising results. However, limitations for their use in clinical trials can be the lack of sufficient amounts and high production costs. Expression of mAbs in the mammary gland of transgenic animals provides an economically advantageous possibility for production of sufficient quantities of a promising antibody for clinical trials and beyond. In this paper, we show the feasibility of this approach, by generating transgenic mice expressing mouse-human chimeric anti-CD19 mAbs in their milk. Mouse anti-CD19 variable (V) region genes were combined with human IgG1 heavy (H) and kappa light (L) chain constant (C) region genes and fused to the bovine beta-lactoglobulin (BLG) promoter in two separate expression cassettes. Co-injection resulted in five transgenic lines. In one of these lines completely assembled chimeric mAbs were secreted into the milk, at an approximate level of 0.5 mg/ml. These mAbs were able to bind specifically to the CD19 surface antigen on human B cells.
van Kuik-Romeijn
P
P
Medical Biotechnology Department, Leiden University, The Netherlands. p.van_kuik@lumc.nl
de Groot
N
N
Hooijberg
E
E
de Boer
H A
HA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000276:immunology; D018941:Antigens, CD19 / Q000276:immunology*; D002417:Cattle; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000378:metabolism; D007782:Lactoglobulins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008892:Milk / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000276:immunology
D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D007782:Lactoglobulins; D011993:Recombinant Fusion Proteins