In Vitro Cellular Cytotoxicity Against Human Bladder Carcinoma Cell Lines

  • A. Böhle
  • A. J. Ulmer
  • M.-H. Wang
  • H.-D. Flad


Clinical trials of intravesical BCG immunotherapy against superficial urothelial bladder carcinoma recurrences have yielded significant results, which seem to be superior to those of intravesical chemotherapy (Herr et al. 1987). However, the mechanisms by which BCG exerts its antitumor effects are still largely unknown. In previous immunohistological examinations we were able to demonstrate the local induction of mononuclear effector cells in the bladder wall such as helper T-cells, macrophages, and B-cells after intravesical BCG (Böhle et al. 1990 a). Furthermore, a significant increase of certain cytokines in the urine, such as interleukin-1, interleukin-2, and tumor necrosis factor, has been detected after intravesical BCG therapy (Haaf et al. 1986; Böhle et al. 1990 b). These findings suggest different possible effector mechanisms which might be involved in tumor rejection. In an attempt to analyse these effects in vitro and obtain more information on their cytotoxic effectiveness against human bladder carcinoma cell lines, we performed a study to evaluate in vitro the cellular cytotoxicity of different mononuclear cells and the cytokines involved.


Bladder Carcinoma Urothelial Carcinoma Cell Bladder Tumor Cell Bladder Carcinoma Cell Line Urothelial Carcinoma Cell Line 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Böhle A, Gerdes J, Ulmer AJ, Hofstetter AG, Flad HD (1990) Effects of local bacillus Calmette-Guérin therapy in patients with bladder carcinoma on immunocompetent cells of the bladder wall. J Urol 144:53–58.PubMedGoogle Scholar
  2. Böhle A, Nowc C, Ulmer AJ, Musehold J, Gerdes J, Hofstetter AG, Flad HD (1990) Elevations of cytokines interleukin-1, interleukin-2, and tumor necrosis factor in the urine of patients after intravesical bacillus Calmette-Guérin immunotherapy. J Urol 144:59–64.PubMedGoogle Scholar
  3. Bosch J vd, Rüller S, Horn D, Schumann R, Schlaak M (1990) Density dependent tumor cell death and reversible cell cycle arrest: mutually exclusive modes of monocyte mediated growth control. Exp Cell Res 187:185–192.PubMedCrossRefGoogle Scholar
  4. El-Demiry MIM, Smith G, Ritchie AWS, James K, Cumming JA, Hargreave TB, Chisholm GD (1987) Local immune responses after intravesical BCG treatment for carcinoma in situ. Br J Urol 60:543.PubMedCrossRefGoogle Scholar
  5. Feist W, Ulmer AJ, Musehold J, Brade H, Kusumoto S, Flad H-D (1989) Induction of tumor necrosis factor α release by lipopolysaccharide and defined lipopolysaccharide partial structures. Immunobiology 179:293–307.PubMedCrossRefGoogle Scholar
  6. Grimm EA, Rosenberg SA (1984) The human lymphokine-activated killer cell phenomenon. Lymphokines 9:279–311.Google Scholar
  7. Guinan P, Shaw M, Ray V (1986) Histopathology of BCG and thiotepa treated bladders. Urol Res 14:211–215.PubMedCrossRefGoogle Scholar
  8. Haaff EO, Catalona WJ, Ratliff TL (1986) Detection of interleukin-2 in the urine of patients with superficial bladder tumors after treatment with intravesical bacillus Calmette-Guérin. J Urol 136:970–974.PubMedGoogle Scholar
  9. Herr HW, Laudone VP, Whitmore WF (1987) An overview of intravesical therapy for superficial bladder tumors. J Urol 138:1363–1368.PubMedGoogle Scholar
  10. Huland E, Huland H (1989) Local continuous high dose interleukin 2: a new therapeutic model for the treatment of advanced bladder carcinoma. Cancer Res 49:5469–5474.PubMedGoogle Scholar
  11. Kelley DR, Haaff EO, Becich M, Lage J, Bauer WC, Dresner SM, Catalona WJ, Ratliff TL (1986) Prognostic value of PPD skin test and granuloma formation in patients treated with intravesical bacillus Calmette-Guérin. J Urol 135:268.PubMedGoogle Scholar
  12. Lotze MT, Matory YL, Ettinghausen SE, Rayner AA, Sharrow SO, Seipp CA, Custer MC, Rosenberg SA (1985) In vivo administration of purified human interleukin 2: II. Half life, immunologic effects, and expansion of peripheral lymphoid cells in vivo with recombinant IL 2. J Immunol 135:2865–2875.PubMedGoogle Scholar
  13. Roberts K, Lotze MT, Rosenberg SA (1987) Separation and functional studies of the human lymphokine-activated killer cell. Cancer Res 47:4366–4371.PubMedGoogle Scholar
  14. Rosenberg SA (1988) Immunotherapy of cancer using interleukin 2: current status and future prospects. Immunol Today 9:58.PubMedCrossRefGoogle Scholar
  15. Sternberg C, Arena M, Pansadoro V, Calabresi F, Haas J, Defidio L, Cusumano G, Carli P, Zeuli M, Rosselli M, Cancrini A (1990) Phase I clinical trial of intravesical recombinant tumor necrosis factor (rTNF) in patients with superficial bladder cancer. Eur Urol [Suppl] 18:410.Google Scholar
  16. Ulmer AJ, Wang M-H, Hua Y, Flad H-D (1990) DNA fragmentation of targets by natural killer cells and cytotoxic macrophages as measured by fluorometric assay using Hoechst dye 33342. J Immunol Methods (in press).Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • A. Böhle
    • 1
  • A. J. Ulmer
    • 2
  • M.-H. Wang
    • 2
  • H.-D. Flad
    • 2
  1. 1.Klinik und Poliklinik für Urologieder Medizinischen UniversitätLübeckGermany
  2. 2.Institut für Experimentelle Biologie und MedizinForschungsinstitut BorstelBorstelGermany

Personalised recommendations