Characterization of a mouse-human chimeric antibody to a cancer-associated antigen

In an attempt to obtain a therapeutic antibody, the murine monoclonal antibody (MAb) MBr1 (IgM,k), directed against human carcinomas, was converted in a mouse/human chimeric MAb of γ1 isotype. The chimeric MAb, γ1 CHI-MBr1, retains the ability to specifically bind tumor cells and tissues with no modification in its binding to the normal material tested. γ1 CHI-MBr1 recognizes mucins and high-molecular-weight glycoproteins carrying the antigenic determinant and stains a neutral glycolipid extracted from MCF-7 cells. The chimeric and the murine MBr1 efficiently cross-inhibit each other on the reference cell line MCF-7 and the calculated affinity constants amount to 3.8 x 10⁷ and 1.7 x 10⁸ M^-1, respectively. The human constant region allows γ1 CHI-MBr1 to bind with the FcR on the human monocytic cell line U937 and to efficiently mediate antibody-dependent cellular cytotoxicity in the presence of human lymphocytes activated by IL2. In addition, γ1 CHI-MBr1, like the murine MBr1, mediates complement-dependent tumor cell lysis. Thus, by modelling a molecule with reduced size and increased functional characteristics, we have obtained a reagent which is more suitable for in vivo therapeutic approaches.