ANTIBODY-INDUCED MODULATION AND INTRACELLULAR-TRANSPORT OF CD10 AND CD19 ANTIGENS IN HUMAN-MALIGNANT B-CELLS

Antibody-induced antigenic modulation (AIAM) is a complex biological p henomenon closely resembling other receptor-ligand interactions. Follo wing exposure to specific antibodies, surface antigens are usually rap idly redistributed on the cell surface and internalized. A subsequent intracellular processing results in dissociation of the antigen-antibo dy complexes, degradation, exocytosis and recycling. AIAM plays an imp ortant role in MoAb-targeted therapy of hematopoietic malignancies con tributing to escape of tumor cells from immunodestruction. On the othe r hand, internalization of MoAbs used as carriers of toxins and drugs is a prerequisite of therapeutic efficacy. Even though MoAbs directed against CD10 and CD19 have been used in immunotherapy of B cell malign ancies, some aspects regarding AIAM of these Ags are not yet fully und erstood. Both Ags are modulated by specific MoAbs and internalized thr ough the same pathway, however, the kinetics of AIAM vary from one Ag to another and from one cell type to another. Recent studies with mali gnant B-cell lines show that, under certain experimental conditions, t he extent and rate of surface clearing, uptake and intracellular trans port are considerably higher in the case of CD19 than in CD10 and high er in less mature cells compared with more mature cells. These observa tions may be useful in the selection of MoAbs for immunotherapy, altho ugh they need to be confirmed with fresh malignant B cells.