Different behaviour of mouse‐human chimeric antibody F(ab') 2 fragments of IgG 1 , IgG 2 and IgG 4 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 IgG 1 , IgG 2 and IgG 4 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 125 I or 131 I 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 IgG 2 sub‐class, whereas F(ab') 2 from chimeric MAb IgG 4 give very low values for these 2 parameters. F(ab') 2 from chimeric MAb IgG 1 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.