Sensitivity of multidrug-resistant tumor cell lines to immunologic effector cells.
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.
Schmidt-Wolf
I G
IG
Abteilung Innere Medizin, Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universitat zu Berlin, Germany.
Lefterova
P
P
Johnston
V
V
Scheffold
C
C
Csipai
M
M
Mehta
B A
BA
Tsuruo
T
T
Huhn
D
D
Negrin
R S
RS
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
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1