Intracellular uptake and catabolism of anti‐IgM antibodies and BI‐specific antibody‐targeted hapten by B‐lymphoma cells

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Abstract
The efficiency of radioimmunotherapy with iodine-labelled antibodies is 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 antibodies to target radiolabelled bivalent haptens to cells. This targeting method has been applied successfully to tumour imaging in colorectal cancer patients and is now considered for therapy. We have investigated the potential of this technique to target iodine radioisotopes by comparing it to targeting with covalently iodine-labelled antibodies in a rapidly internalising antigenic system, the surface IgM of a B-lymphoma cell line. A 5-fold increase in the intracellular retention time of activity as compared to l25l-labelled F(ab')2 or IgG was observed. The radiolabelled hapten did not undergo any catabolism after internalisation. Resistance to cellular proteases and failure of recognition of the hapten by amino acid transporter systems may be potential explanations for these observations. This should make non-covalent targeting, particularly the AES, a method of choice to target modulating antigens for the therapy of malignant hemopathies.