Susceptibility of multidrug-resistant human T-lymphoblastoid CEM cell line to cell-mediated cytolysis.
The using of multidrug-resistant (MDR) cell variants represents one of the major obstacles to an effective cancer therapy based on the administration of cytotoxic compounds. In the present article we describe experimental procedures able to eradicate, in vitro, by using specific immunological reagent, MDR tumor cells. In an allogeneic cell system, natural killer (NK) and lymphokine activated killer (LAK) cells result effective against MDR variants of the human T-lymphoblastoid CEM cell line. Surprisingly effector cells discriminate in their lytic capacity target cells possessing a MDR phenotype. A direct relationship between the degree of relative resistance shown by target cells and cytotoxic level exerted by peripheral lymphocytes stimulated and non by IL-2 was observed. The preincubation of MDR cell variants with a monoclonal antibody (MoAb57) specific for an extramembranal epitope of P-glycoprotein induced, in presence of effector cells, a strong antibody-dependent cell-mediated cytolysis (ADCC). This phenomenon was observed only in MDR variants over-expressing in concomitance with drug-resistance high level of P-glycoprotein. In identical experimental conditions, drug-sensitive parental cells does not show valuable ADCC.
Ramoni
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C
Laboratorio di Immunologia, Istituto Superiore di Sanità, Rome, Italy.
Dupuis
M L
ML
Cenciarelli
C
C
Ciccolini
F
F
Cianfriglia
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000920:Antibody-Dependent Cell Cytotoxicity; D004273:DNA, Neoplasm / Q000032:analysis; D004351:Drug Resistance; D005434:Flow Cytometry; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004273:DNA, Neoplasm; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D014747:Vinblastine