INTRACELLULAR UPTAKE AND CATABOLISM OF ANTI-IGM ANTIBODIES AND BI-SPECIFIC ANTIBODY-TARGETED HAPTEN BY B-LYMPHOMA CELLS

The efficiency of radioimmunotherapy with iodine-labelled antibodies i s often limited by intracellular internalisation and catabolism after initial binding to the cellular targets. We have developed a technique called affinity enhancement system (AES) which uses bi-specific antib odies to target radiolabelled bivalent haptens to cells. This targetin g method has been applied successfully to tumour imaging in colorectal cancer patients and is now considered for therapy. We have investigat ed the potential of this technique to target iodine radioisotopes by c omparing it to targeting with covalently iodine-labelled antibodies in a rapidly internalising antigenic system, the surface IgM of a B-lymp homa cell line. A 5-fold increase in the intracellular retention time of activity as compared to I-125-labelled F(ab')(2) or IgG was observe d. The radiolabelled hapten did not undergo any catabolism after inter nalisation. Resistance to cellular proteases and failure of recognitio n of the hapten by amino acid transporter systems may be potential exp lanations for these observations. This should make noncovalent targeti ng, particularly the AES, a method of choice to target modulating anti gens for the therapy of malignant hemopathies. (C) 1995 Wiley-Liss, In c.