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Potentiation of human natural killer cell activity by recombinant interleukin-2 towards multidrug-resistant human
E W Ades1, D Bosse, J Pruckler
1Biological Products Branch, Centers for Disease Control, US Department of Health and Human Services, Atlanta, Ga.
Abstract:
Relatively little is understood about the antigen recognition and target structures used by natural killer (NK) cells. The purpose of this study was to analyze the relationship of a multidrug-resistant cell line expressing the P-glycoprotein (GP170 surface glycoprotein) derived from the parent non-drug-resistant malignant tumor cell line for susceptibility to lysis by either NK or lymphokine-activated killer cells. Our results demonstrate no significant difference in NK activity against either the non-drug-resistant or drug-resistant malignant cell line; Interleukin-2 induces a significant increase in cytolytic activity toward the multidrug-resistant cell line. These data suggest that malignant cells refractory to treatment or occurring after successful treatment are susceptible to immunotherapeutic intervention.
Insights
Natural killer (NK) cells show similar activity against drug-resistant and non-drug-resistant cancer cells. However, Interleukin-2 enhances NK cell activity, suggesting immunotherapy potential for refractory cancers.
Area of Science:
- Immunology
- Cancer Biology
- Cellular Biology
Background:
- Natural killer (NK) cells are crucial for innate immunity, but their antigen recognition and target structures remain incompletely understood.
- Multidrug resistance (MDR) in cancer poses a significant therapeutic challenge, often involving cell surface glycoproteins like P-glycoprotein (GP170).
Purpose of the Study:
- To investigate the susceptibility of a multidrug-resistant (MDR) cell line expressing P-glycoprotein (GP170) to lysis by NK and lymphokine-activated killer (LAK) cells.
- To compare NK cell activity against both drug-resistant and non-drug-resistant malignant cell lines.
Main Methods:
- Generation of a multidrug-resistant malignant cell line expressing P-glycoprotein (GP170) from a parent non-drug-resistant line.
- Assays to measure the cytolytic activity of natural killer (NK) cells and lymphokine-activated killer (LAK) cells against both cell lines.
- Treatment with Interleukin-2 to assess its effect on cytolytic activity.
Main Results:
- No significant difference was observed in NK cell activity against the non-drug-resistant and the multidrug-resistant malignant cell lines.
- Interleukin-2 treatment significantly increased the cytolytic activity of NK cells toward the multidrug-resistant cell line.
Conclusions:
- Malignant cells, even those refractory to conventional treatments, are susceptible to immunotherapeutic interventions.
- NK cell-based immunotherapies, particularly when augmented with agents like Interleukin-2, show promise for treating drug-resistant cancers.