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) MBrI (IgM,k), directed against human carcinomas, was converted in a mouse/human chimeric MAb of gamma I isotype. The chimeric MAb, gamma I CHI-MBrI, retains the ability to specifically bind tumor cells and tissues with no modification in its binding to the normal material tested. gamma I CHI-MBrI 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 MBrI efficiently cross-inhibit each other on the reference cell line MCF-7 and the calculated affinity constants amount to 3.8 x 10(7) and 1.7 x 10(8) M-1, respectively. The human constant region allows gamma I CHI-MBrI 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, gamma I CHI-MBrI, like the murine MBrI, 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.
Orlandi
R
R
Istituto Nazionale per lo Studio e la Cura dei Tumori, Division of Experimental Oncology, Milan, Italy.
Figini
M
M
Tomassetti
A
A
Canevari
S
S
Colnaghi
M I
MI
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000276:immunology; D001667:Binding, Competitive; D006801:Humans; D051379:Mice; D011961:Receptors, Fc / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000276:immunology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins