Journal article
Immunotherapy of experimental bladder cancer with recombinant BCG expressing interferon-γ
Journal of immunotherapy (1997), Vol.27(2), pp.116-123
2004
DOI: 10.1097/00002371-200403000-00005
PMID: 14770083
Abstract
One of the most potent immunotherapies presently used is the application of Bacillus Calmette Guérin (BCG) to prevent recurrences of superficial bladder cancer. Despite its successful use, nonresponders and certain side effects remain a major obstacle. Therefore, current studies aim at developing recombinant BCG (rBCG) strains to further improve the effectiveness of the therapy. In BCG-treated patients a strong local induction of Th1-like cytokines was observed. For this reason rBCG-strains secreting Th1-like cytokines might be potentially useful agents to improve this type of immunotherapy. Because we previously demonstrated the essential role of IFNγ in BCG-induced antitumor responses, in this study a rBCG strain secreting murine IFNγ (rBCG-IFNγ) was generated and tested for its immunostimulatory capacity in several in vitro and in vivo test systems. In vitro rBCG-IFNγ specifically up-regulated expression of MHC class I molecules on a murine bladder cancer cell line (MB49), compared to the rBCG control strain (transfected with an empty vector). In a murine model of experimental bladder cancer, intravesical instillation of rBCG-IFNγ resulted in an enhanced recruitment of CD4+ T-cells into the bladder and further induced the local expression of IL-2 and IL-4 cytokines (mRNA) compared to control rBCG. With a low-dose treatment regimen for murine orthotopic bladder cancer, rBCG-IFNγ significantly prolonged survival, whereas the therapeutic effect of wild-type control BCG did not reach statistical significance. We conclude that this recombinant BCG strain has enhanced immunostimulatory potential and might offer new opportunities in the treatment of bladder cancer.
Details
- Title: Subtitle
- Immunotherapy of experimental bladder cancer with recombinant BCG expressing interferon-γ
- Creators
- Judith ARNOLD - Research Center Borstel, Division of Immunotherapy, Borstel, GermanyElizabeth C DE BOER - Academic Medical Center, University of Amsterdam, Department of Urology, Amsterdam, NetherlandsMichael A O'DONNELL - University of Iowa, Department of Urology, Iowa City, IA, United StatesAndreas BÖHLE - Helios Agnes Karll Hospital, Bad Schwartau, GermanySven BRANDAU - Research Center Borstel, Division of Immunotherapy, Borstel, Germany
- Resource Type
- Journal article
- Publication Details
- Journal of immunotherapy (1997), Vol.27(2), pp.116-123
- Publisher
- Lippincott; Hagerstown, MD; Philadelphia,PA
- DOI
- 10.1097/00002371-200403000-00005
- PMID
- 14770083
- ISSN
- 1524-9557
- eISSN
- 1537-4513
- Language
- English
- Date published
- 2004
- Academic Unit
- Urology
- Record Identifier
- 9984051753102771
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