ALTERED PHARMACOKINETIC AND TUMOR-LOCALIZATION PROPERTIES OF FAB' FRAGMENTS OF A MURINE MONOCLONAL ANTI-CEA ANTIBODY BY COVALENT MODIFICATION WITH LOW-MOLECULAR-WEIGHT DEXTRAN

This paper describes the modification of Fab' fragments of ZCE025, a m urine monoclonal antibody recognizing carcinoembryonic antigen (CEA), with oxidized dextran of low molecular weight. This modification alter ed the in vitro and in vivo characteristics of the Fab'. The dextran c onjugated fragments exhibited markedly reduced renal uptake and excret ion and the prolonged residence time of the Fab' in the vascular compa rtment. The result was enhanced tumour localization of the derivative compounds compared with underivatized Fab', even though the process of chemical coordination reduced the immunoreactivity of the molecule. T he isoelectric point of the molecule was much lower than the unaltered Fab' and previous research has shown this to reduce markedly its pote ntial for inducing a human anti-mouse antibody (HAMA) response. Thus, the conjugation of Fab' fragments with low molecular weight oxidized d extrans can increase the bioavailability of these fragments for tumour localization, while simultaneously reducing their immunogenic potenti al and renal accumulation problems.