Susceptibility of multidrug-resistant human leukemia cell lines to human interleukin 2-activated killer cells.
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.
Kimmig
A
A
Department of Hematology and Oncology, Children's University Hospital, Tuebingen, West Germany.
Gekeler
V
V
Neumann
M
M
Frese
G
G
Handgretinger
R
R
Kardos
G
G
Diddens
H
H
Niethammer
D
D
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019011:Antigens, CD7; D000943:Antigens, Differentiation / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D004351:Drug Resistance; D015972:Gene Expression Regulation, Neoplastic; D006649:Histocompatibility Antigens / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology*; D007938:Leukemia / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D017493:Leukocyte Common Antigens; D016256:Lewis X Antigen; D008562:Membrane Glycoproteins / Q000235:genetics; D010641:Phenotype; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019011:Antigens, CD7; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D006649:Histocompatibility Antigens; D007376:Interleukin-2; D016256:Lewis X Antigen; D008562:Membrane Glycoproteins; D014700:Verapamil; D017493:Leukocyte Common Antigens