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

✍ Scribed by R. Orlandi; M. Figini; A. Tomassetti; S. Canevari; M. I. Colnaghi

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: French
• Weight: 639 KB
• Volume: 52
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910520417

✦ Synopsis

In an attempt to obtain a therapeutic antibody, the murine monoclonal antibody (MAb) MBr I (IgM,k), directed against human carcinomas, was converted in a mouse/human chimeric MAb of y l isotype. The chimeric MAb, y l CHI-MBrl, retains the ability to specifically bind tumor cells and tissues with no modification in its binding to the normal material tested. yl CHI-MBr I 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 MBrl efficiently cross-inhibit each other on the reference cell line MCF-7 and the calculated affinity constants amount to 3.8 X I O7 and I .7 x I O8 M-I, respectively. The human constant region allows ylCHI-MBrl 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, y l CHI-MBr I, like the murine MBr I, mediates complement-dependent turnorcell 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.