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 tri als 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 provid es an economically advantageous possibility for production of sufficient qu antities of a promising antibody for clinical trials and beyond. In this pa per, we show the feasibility of this approach, by generating transgenic mic e 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 bet a-lactoglobulin (BLG) promoter in two separate expression cassettes. Co-inj ection resulted in five transgenic lines. In one of these lines completely assembled chimeric mAbs were secreted into the milk, at an approximate leve l of 0.5 mg/ml. These mAbs were able to bind specifically to the CD19 surfa ce antigen on human B cells.