title: Sensitivity of multidrug-resistant tumor cell lines to immunologic effector cells.
abstract: The ability of malignant cells to survive exposure to cytotoxic agents is a major obstacle to cure in patients with cancer. Multidrug resistance and the expression of P-glycoprotein are emerging as a cause of chemotherapy failure. Immunologic effector cells such as lymphokine-activated killer (LAK) cells or cytokine-induced killer (CIK) cells are capable of killing a broad range of tumor cell lines or freshly isolated tumor cells. As demonstrated here, LAK, and CIK cells possess a high level of cytotoxic activity against tumor cell lines both resistant and sensitive to chemotherapeutic agents such as doxorubicin or vinblastine. CIK cells possessed a higher level of cytotoxic activity than LAK cells as determined by 51Cr release and a tumor colony assay. Monoclonal antibodies against P-glycoprotein did not block the lysis of tumor cells resistant to chemotherapy by CIK cells. In contrast, antibodies to LFA-1 and ICAM-1 blocked CIK cell-mediated tumor cell lysis. These data demonstrate that immunological approaches to cancer therapy may be useful in overcoming disease caused by drug resistance.
authors.affiliation: Abteilung Innere Medizin, Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universitat zu Berlin, Germany.
authors.forename: I G
authors.initials: IG
authors.lastname: Schmidt-Wolf
authors.forename: P
authors.initials: P
authors.lastname: Lefterova
authors.forename: V
authors.initials: V
authors.lastname: Johnston
authors.forename: C
authors.initials: C
authors.lastname: Scheffold
authors.forename: M
authors.initials: M
authors.lastname: Csipai
authors.forename: B A
authors.initials: BA
authors.lastname: Mehta
authors.forename: T
authors.initials: T
authors.lastname: Tsuruo
authors.forename: D
authors.initials: D
authors.lastname: Huhn
authors.forename: R S
authors.initials: RS
authors.lastname: Negrin
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000276:immunology; D016923:Cell Death / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D018432:Drug Resistance, Multiple / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000473:pathology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1