Anti-CD19 antibodies inhibit the function of the P-gp pump in multidrug-resistant B lymphoma cell

after chemotherapy, tumor tells with multidrug resistance (MDR) often emerg e. MDR is attributable to the expression of membrane transport proteins tha t inhibit the cellular influx and increase the efflux of many chemotherapeu tic drugs. One such protein is P-glycoprotein (P-gp), which functions as an ATP-dependent active transporter. Recently, an anti-P-gp monoclonal antibo dy (MAb) that inhibits P-gp has been described. Previous studies from our l aboratory using the anti-CD19 B-cell lymphoma-reactive MAb, HD37, have sugg ested that HD37 may also influence MDR, To test this directly, we used Nama lwa/MDR1 cells to study the effect of HD37 on the efflux of rhodamine 123 f rom these cells, We found that HD37 and three other anti-CD19 MAbs inhibite d the efflux of rhodamine 123 from Namalwa/MDR1 cells with similar to 50% o f the efficiency of the well-known chemosensitizer, verapamil. In contrast, MAbs against seven other molecules expressed on these cells were ineffecti ve. The inhibitory activity of HD37 did not require an Fc portion; F(ab')(2 ) fragments were effective, but Fab' fragments were not, suggesting Chat hi gher avidity binding and/or cross-linking of CD19 are necessary. We could f ind no evidence that HD37 recognizes a cross-reactive epitope on P-gp, modu lates P-gp from the cell surface, or enhances the ATPase activity of membra nes from treated cells.