Different behaviour of mouse-human chimeric antibody F(ab')2 fragments of IgG1, IgG2 and IgG4 sub-classin vivo (original) (raw)

1992, 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'), fragments were obtained by pepsin digestion of the purified chimeric MAbs of human IgG,, IgG, and IgG, sub-class and of parental mouse MAb IgG,. The 4 F(ab'), fragments exhibit similar molecular weight by SDS-PAGE. They were labelled with I2'l or "'I and high binding (80 to 87Yo) 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'), from chimeric MAb of human IgG, sub-class, whereas F(ab'), from chimeric MAb IgG, give very low values for these 2 parameters. F(ab'), from chimeric MAb IgG, 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'), to be used for tumour detection by immunoscintigraphy and for radioimmunotherapy.