AbstractIn an attempt to obtain a therapeutic antibody, the murine monoclonal antibody (MAb) MBr 1 (IgM, k), directed against human carcinomas, was converted in a mouse/human chimeric MAb of γ I isotype. The chimeric MAb, γICHI‐MBr 1, retains the ability to specifically bind tumor cells and tissues with no modification in its binding to the normal material tested. γI CHI‐MBr 1 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 MBr 1 efficiently cross‐inhibit each other on the reference cell line MCF‐7 and the calculated affinity constants amount to 3.8 × 107 and 1.7 × 108M−1, respectively. The human constant region allows γI CHI‐MBr 1 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, γICHI‐MBr 1, like the murine MBr I, 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. © 1992 Wiley‐Liss, Inc.
