Modulation of P-glycoprotein-mediated multidrug resistance by monoclonal antibodies, immunotoxins or antisense oligodeoxynucleotides in kidney carcinoma and normal kidney cells.

In the present investigation we show that both monoclonal antibodies against P-170 (265/F4, MRK 16, and HYB 612) and 265/F4-ricin alpha-chain immunotoxin are useful tools for the eradication of kidney carcinoma and normal kidney primary cell cultures with high P-170 expression, whereas kidney tumor and normal kidney cell lines with low amounts of P-170 are less affected. Furthermore, we found that the expression of P-170 in both kidney tumor and normal kidney cell cultures with high amounts of P-170 was inhibited by antisense oligodeoxynucleotides complementary to base pairs -9 to +6 of the MDR1 gene. These data indicate that these approaches for the eradication of P-170 expressing multidrug-resistant cells are not limited to tumors but also affect P-170 expressing normal cells.