MONOCLONAL-ANTIBODIES TO GLYCOPROTEINS OF VINCA ALKALOID-RESISTANT HUMAN-LEUKEMIC CELLS

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (7) , 3220-3224
Abstract
Drug resistance is a major problem in the successful treatment of cancer. Resistance to one drug is often associated with cross-resistance to other anticancer agents. This is commonly seen with the natural product anticancer drugs such as the Vinca alkaloids and anthracyclines. In experimental systems, specific changes in plasma membranes characterize this multiple drug resistance. The most prominent of these is the enhanced expression in several systems of high-MW glycoproteins ranging from MW .apprxeq. 150,000 to .apprxeq.180,000, the amount ofwhich has been related to the degree of drug resistance. The production of 3 monoclonal antibodies that bind preferentially to the surfaces of cultured human leukemic lymphoblasts resistant to the Vinca alkaloid vinblastine is reported. Each antibody recognizes a surface membrane glycoprotein with MW of 180,000 to 210,000. Additionally, 2 of the antibodies also recognize a 2nd surface glycoprotein with MW of either .apprxeq. 155,000 or .apprxeq. 130,000. All of these glycoproteins areoverexpressed in the alkaloid-resistant cells. While a MW .apprxeq. 180,000 protein was associated with multiple drug resistance, the other 2 glycoproteins have not been described previously in these cells. These antibodies may be useful in studies of mechanisms of drug resistance, as well as in screening cells from drug-resistant patients for these resistance-associated glycoproteins.