Susceptibility of multidrug-resistant human leukemia cell lines to human interleukin 2-activated killer cells

• Published in: Cancer research (Chicago, Ill.) Vol. 50; no. 21; pp. 6793 - 6799
• Main Authors: KIMMIG, A, GEKELER, V, NEUMANN, M, FRESE, G, HANDGRETINGER, R, KARDOS, G, DIDDENS, H, NIETHAMMER, D
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.11.1990
• Subjects: Antigens, CD7; Antigens, Differentiation - immunology; Antigens, Differentiation, T-Lymphocyte - immunology; Antineoplastic agents; ATP-Binding Cassette, Sub-Family B, Member 1; Biological and medical sciences; Drug Resistance; Gene Expression Regulation, Neoplastic; General aspects; Histocompatibility Antigens - immunology; Humans; Immunotherapy, Adoptive; Interleukin-2 - pharmacology; Killer Cells, Lymphokine-Activated - physiology; Leukemia - genetics; Leukemia - immunology; Leukemia - therapy; Leukocyte Common Antigens; Lewis X Antigen; Medical sciences; Membrane Glycoproteins - genetics; Pharmacology. Drug treatments; Phenotype; Tumor Cells, Cultured; Verapamil - pharmacology; Human; Phenotype; Sensitivity resistance; Leukemia; Multiple resistance; LAK cell; T-Lymphocyte; Cytotoxicity; Malignant hemopathy; In vitro; Tumor cell
• ISSN: 0008-5472; 1538-7445

Considering the possibility to overcome drug resistance by other treatment strategies than chemotherapy we investigated the susceptibility of three independently selected multidrug-resistant sublines of the T-lymphoblastoid leukemic cell line CCRF-CEM to lymphokine-activated killer (LAK) cells. We found that two of the multidrug-resistant sublines were significantly less susceptible targets to LAK cells. A third one, however, was as susceptible as the parental CCRF-CEM cell line. Moreover, a multidrug-resistant subline that reverted to an almost drug-sensitive phenotype was observed to be also revertant for resistance against LAK cells. We found an inverse relationship between the expression of the mdr1 gene (P-glycoprotein) and the susceptibility to LAK cells. Verapamil, a calcium channel blocker, while increasing the drug sensitivity of a multidrug-resistant subline, did not induce a reversal of the suppression of LAK susceptibility. The possibility of enhanced resistance to LAK cells of multidrug-resistant cells should be taken into account when one is looking for therapy strategies to overcome multidrug resistance.