Different behaviour of mouse‐human chimeric antibody F(ab')2 fragments of IgG1, IgG2 and IgG4 sub‐class in vivo

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 trans‐ fected 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 IgG. 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.