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Dissecting the Immunobiological Effects of Bacillus Calmette-Guérin (BCG) In Vitro: Evidence of a Distinct BCG-Activated Killer (BAK) Cell Phenomenon

1993; Lippincott Williams & Wilkins; Volume: 150; Issue: 6 Linguagem: Inglês

10.1016/s0022-5347(17)35941-4

1527-3792

Andreas Böhle, A. Thanhäuser, A.J. Ulmer, Martin Ernst, H.‐D. Flad, D. Jocham,

Epigenetics and DNA Methylation

No AccessJournal of Urology1 Dec 1993Dissecting the Immunobiological Effects of Bacillus Calmette-Guérin (BCG) In Vitro: Evidence of a Distinct BCG-Activated Killer (BAK) Cell Phenomenon A. Böhle, A. Thanhäuser, A.J. Ulmer, M. Ernst, H.-D. Flad, and D. Jocham A. BöhleA. Böhle , A. ThanhäuserA. Thanhäuser , A.J. UlmerA.J. Ulmer , M. ErnstM. Ernst , H.-D. FladH.-D. Flad , and D. JochamD. Jocham View All Author Informationhttps://doi.org/10.1016/S0022-5347(17)35941-4AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Several immunobiological effects of intravesical bacillus Calmette-Guérin (BCG) during immunotherapy of superficial bladder cancer have been suggested as possible mediators of the mode of action. In an attempt to elucidate which of these effects is relevant to tumoricidal activity, an in vitro cytotoxicity assay was employed in which the direct effects of BCG and of cytokines against four transitional carcinoma cell lines were studied. Furthermore, peripheral blood mononuclear cells (PBMNC) were analyzed for their cytotoxic potential against these target cells. We found that none of the cytokines interleukin-1, interleukin-2, interferon-gamma, tumor necrosis factor alpha, lymphotoxin, or BCG alone were cytotoxic against the bladder carcinoma cell lines. However, a pronounced cytotoxicity against these targets resistant to natural killer cells could be induced in PBMNC by coincubation with viable BCG. We termed this the BCG-activated killer (BAK) cell phenomenon. In contrast to lymphokine-activated (LAK) cells, these BAK cells needed prolonged activation for 7 days and did not enhance the cytotoxicity against K562 target cells sensitive to natural killer cells. Nonviable, heat-inactivated BCG was significantly less effective, and sonificated fractions of BCG were not effective in stimulating PBMNC towards BAK cell activity. In vitro dissection of effects observed during BCG intravesical therapy may give more insight into the mode of action of BCG and may help to separate primary tumoricidal effector mechanisms from secondary concomitant phenomena. Further characterization of the BAK cell may result in an improvement of intravesical BCG immunotherapy. © 1993 by The American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited bySecanella-Fandos S, Noguera-Ortega E, Olivares F, Luquin M and Julián E (2013) Killed but Metabolically Active Mycobacterium bovis bacillus Calmette-Guérin Retains the Antitumor Ability of Live bacillus Calmette-GuérinJournal of Urology, VOL. 191, NO. 5, (1422-1428), Online publication date: 1-May-2014.KAASINEN E, HARJU L and TIMONEN T (2018) Inhibition Of Natural, Interleukin-2 Stimulated and Bacillus Calmette-Guerin Enhanced Cytotoxicity With Anti-CD16 AntibodiesJournal of Urology, VOL. 167, NO. 5, (2209-2214), Online publication date: 1-May-2002.Soloway M, Sofer M and Vaidya A (2018) Contemporary Management Of Stage T1 Transitional Cell Carcinoma Of The BladderJournal of Urology, VOL. 167, NO. 4, (1573-1583), Online publication date: 1-Apr-2002.SAINT F, PATARD J, MAILLE P, SOYEUX P, HOZNEK A, SALOMON L, ABBOU C and CHOPIN D (2018) PROGNOSTIC VALUE OF A T HELPER 1 URINARY CYTOKINE RESPONSE AFTER INTRAVESICAL BACILLUS CALMETTE-GUERIN TREATMENT FOR SUPERFICIAL BLADDER CANCERJournal of Urology, VOL. 167, NO. 1, (364-367), Online publication date: 1-Jan-2002.BÖHLE A, BÜTTNER H and JOCHAM D (2018) PRIMARY TREATMENT OF CONDYLOMATA ACUMINATA WITH VIABLE BACILLUS CALMETTE-GUERINJournal of Urology, VOL. 165, NO. 3, (834-836), Online publication date: 1-Mar-2001.BRAKE M, LOERTZER H, HORSCH R and KELLER H (2018) RECURRENCE AND PROGRESSION OF STAGE T1, GRADE 3 TRANSITIONAL CELL CARCINOMA OF THE BLADDER FOLLOWING INTRAVESICAL IMMUNOTHERAPY WITH BACILLUS CALMETTE-GUERINJournal of Urology, VOL. 163, NO. 6, (1697-1701), Online publication date: 1-Jun-2000.KAASINEN E, HARJU L, ALFTHAN O and TIMONEN T (2018) NON-SPECIFIC, RAPIDLY GENERATED CYTOTOXICITY IN LYMPHOCYTES INDUCED BY BCG IN VITRO: NO EVIDENCE OF ENHANCING EFFECT FROM PRECEDING INTERACTION BETWEEN BCG AND TRANSITIONAL CELL LINE CELLSJournal of Urology, VOL. 163, NO. 1, (317-322), Online publication date: 1-Jan-2000.DUREK C, BRANDAU S, ULMER A, FLAD H, JOCHAM D and BOHLE A (2018) BACILLUS-CALMETTE-GUERIN (BCG) AND 3D TUMORS: AN IN VITRO MODEL FOR THE STUDY OF ADHESION AND INVASIONJournal of Urology, VOL. 162, NO. 2, (600-605), Online publication date: 1-Aug-1999.ZHANG Y, KHOO H and ESUVARANATHAN K (2018) EFFECTS OF BACILLUS CALMETTE-GUERIN AND INTERFERON alpha-2B ON CYTOKINE PRODUCTION IN HUMAN BLADDER CANCER CELL LINESJournal of Urology, VOL. 161, NO. 3, (977-983), Online publication date: 1-Mar-1999.Bohle A, Rusch-Gerdes S, Ulmer A, Braasch H and Jocham D (2018) The Effect of Lubricants on Viability of Bacillus Calmette-Guerin for Intravesical Immunotherapy Against Bladder CarcinomaJournal of Urology, VOL. 155, NO. 6, (1892-1896), Online publication date: 1-Jun-1996.de Reijke T, de Boer E, Kurth K and Schamhart D (2018) Urinary Cytokines During Intravesical Bacillus Calmetteguerin Therapy for Superficial Bladder Cancer: Processing, Stability and Prognostic ValueJournal of Urology, VOL. 155, NO. 2, (477-482), Online publication date: 1-Feb-1996. Volume 150 Issue 6 December 1993 Page: 1932-1937 Advertisement Copyright & Permissions© 1993 by The American Urological Association Education and Research, Inc.KeywordsBCG vaccinebladder neoplasmsimmunotherapykiller cells, naturalMetrics Author Information A. Böhle More articles by this author A. Thanhäuser More articles by this author A.J. Ulmer More articles by this author M. Ernst More articles by this author H.-D. Flad More articles by this author D. Jocham More articles by this author Expand All Advertisement PDF downloadLoading ...