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Table of Contents
Vol. 39, No. 5, 2001
Issue release date: May 2001
Section title: Bladder and Urothelial Cancer
Eur Urol 2001;39:518–524
(DOI:10.1159/000052497)

Activation of Natural Killer Cells by Bacillus Calmette–Guérin

Brandau S.a · Böhle A.a, b
aDivision of Immunotherapy, Research Center Borstel, and bDepartment of Urology, Medical University of Lübeck, Germany

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Article / Publication Details

First-Page Preview
Abstract of Bladder and Urothelial Cancer

Published online: May 14, 2001
Issue release date: May 2001

Number of Print Pages: 7
Number of Figures: 3
Number of Tables: 1

ISSN: 0302-2838 (Print)
eISSN: 1421-993X (Online)

For additional information: http://www.karger.com/EUR

Abstract

Objectives: Using a human in vitro model we have previously identified so–called bacillus Calmette–Guérin (BCG)–activated killer (BAK) cells as potential effector cells in BCG immunotherapy. This study was designed to prove the hypothesis that BAK cells are a subpopulation of natural killer (NK) cells and to analyze the role of NK cells during BCG immunotherapy in vivo. Methods: After stimulation of mononuclear cells (MNCs) with BCG for 7 days CD3+ and CD56+ lymphocytes were depleted by magnetic cell separation. Subsequently, the cytotoxicity of the marker–negative cell population was tested in a radioactive release assay. Coexpression of CD56/CD16 and CD56/perforin was assessed by flow cytometry. The importance of NK cells for effective BCG immunotherapy in vivo was analyzed by comparing BCG treatment of bladder tumors bearing ‘wild–type’ C57BL/6 and NK–deficient beige mice. Results: BAK cells were shown to have a CD3–/CD56+ NK cell phenotype. They expressed high amounts of perforin and low amounts of CD16, both of which are characteristic features of (activated) NK cells. BCG immunotherapy significantly prolonged survival in tumor–bearing C57BL/6 mice but was ineffective in NK–deficient beige mice. However, BCG treatment did not influence the frequency of pulmonary metastases in both mouse strains. Conclusions: Our data clearly indicate that stimulation of human MNCs with BCG leads to the activation of cytotoxic lymphocytes with NK cell phenotype. These killer cells express perforin and CD16, two molecules involved in NK cell cytotoxicity. Finally, ineffective BCG treatment of beige mice suggests a key role for NK cells during BCG immunotherapy in vivo.


Article / Publication Details

First-Page Preview
Abstract of Bladder and Urothelial Cancer

Published online: May 14, 2001
Issue release date: May 2001

Number of Print Pages: 7
Number of Figures: 3
Number of Tables: 1

ISSN: 0302-2838 (Print)
eISSN: 1421-993X (Online)

For additional information: http://www.karger.com/EUR


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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