Open AccessA monoclonal antibody-Pseudomonas toxin conjugate that specifically kills multidrug-resistant cells.
Author(s) -
David J. FitzGerald,
Mark C. Willingham,
Carol O. Cardarelli,
Hirofumi Hamada,
Takashi Tsuruo,
Michael M. Gottesman,
Ira Pastan
Publication year - 1987
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.84.12.4288
Subject(s) - multiple drug resistance , monoclonal antibody , p glycoprotein , efflux , antibody , toxin , conjugate , biology , drug resistance , microbiology and biotechnology , glycoprotein , immunotoxin , cancer cell , cancer , immunology , biochemistry , mathematical analysis , genetics , mathematics
One form of multidrug resistance is due to the expression of a 170-kDa energy-dependent drug efflux pump called P-glycoprotein in the plasma membranes of human cancer cells. We have prepared conjugates of Pseudomonas toxin with the anti-P-glycoprotein monoclonal antibody MRK-16. These anti-P-glycoprotein-toxin conjugates specifically kill multidrug-resistant human KB cells. Similar conjugates could be useful in cancer therapy to reduce or eliminate multidrug-resistant tumor populations in tumors intrinsically resistant to chemotherapy or in populations that become resistant during combination chemotherapy.