Article: article from journal or magazin.
Different behaviour of mouse-human chimeric antibody F(ab')2 fragments of IgG1, IgG2 and IgG4 sub-class in vivo.
International Journal of Cancer
Mouse-human chimeric monoclonal antibodies (MAbs) of 3 different human IgG sub-classes directed against carcinoembryonic antigen (CEA) have been produced in SP-0 cells transfected with genomic chimeric DNA. F(ab')2 fragments were obtained by pepsin digestion of the purified chimeric MAbs of human IgG1, IgG2 and IgG4 sub-class and of parental mouse MAb IgG1. The 4 F(ab')2 fragments exhibit similar molecular weight by SDS-PAGE. They were labelled with 125I or 131I and high binding (80 to 87%) to purified unsolubilized CEA was observed. In vivo, double labelling experiments indicate that the longest biological half-life and the highest tumour-localization capacity is obtained with F(ab')2 from chimeric MAb of human IgG2 sub-class, whereas F(ab')2 from chimeric MAb IgG4 give very low values for these 2 parameters. F(ab')2 from chimeric MAb IgG1 and from parental mouse MAb yield intermediate results in vivo. Our findings should help to select the appropriate human IgG sub-class to produce chimeric or reshaped MAb F(ab')2 to be used for tumour detection by immunoscintigraphy and for radioimmunotherapy.
Animals, Antibodies, Monoclonal/chemistry, Antibodies, Monoclonal/genetics, Antibody Affinity, Carcinoembryonic Antigen/immunology, Colonic Neoplasms/immunology, Humans, Immunoglobulin Fab Fragments/chemistry, Immunoglobulin Fab Fragments/immunology, Immunoglobulin G/genetics, Immunoglobulin G/immunology, Mice, Mice, Nude, Neoplasm Transplantation, Recombinant Fusion Proteins/immunology, Structure-Activity Relationship
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