ArticleClinical and experimental immunology2004
Recombinant Mycobacterium bovis bacillus Calmette-Guérin (BCG) expressing mouse IL-18 augments Th1 immunity and macrophage cytotoxicity.
Article in Clinical and experimental immunology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 79 citations in OpenAlex.
- Bioengineering strategies to enhance BCG immunotherapy against bladder cancer.Frontiers in immunology · 2026Review
- BCG therapy in bladder cancer and its tumor microenvironment interactions.Clinical microbiology reviews · 2025Review
- Recombinant BCG Expressing IL-12 as A Novel Immunomodulatory Strategy for Allergic Asthma: Opportunities and Challenges.Clinical reviews in allergy & immunology · 2025Review
- Bladder cancer immunotherapy parallel advances in BCG optimization and next-generation vaccine platforms.Frontiers in immunology · 2025Review
- Nano-Bacillus Calmette-Guérin immunotherapies for improved bladder cancer treatment.Journal of Zhejiang University. Science. B · 2024Review
- Detailed Structural Analysis of the Immunoregulatory Polysaccharides from the Mycobacterium Bovis BCG.Molecules (Basel, Switzerland) · 2022Article
- Recombinant BCG to Enhance Its Immunomodulatory Activities.Vaccines · 2022Review
- Article
- FimH confers mannose-targeting ability to Bacillus Calmette-Guerin for improved immunotherapy in bladder cancer.Journal for immunotherapy of cancer · 2022Article
- BCG as a Vector for Novel Recombinant Vaccines against Infectious Diseases and Cancers.Vaccines · 2020Article
- The multifaceted immune regulation of bladder cancer.Nature reviews. Urology · 2019Review
- Deletion of BCG Hip1 protease enhances dendritic cell and CD4 T cell responses.Journal of leukocyte biology · 2018Article
- Next-Generation Vaccines Based on Bacille Calmette-Guérin.Frontiers in immunology · 2018Review
- RecombinantExperimental and therapeutic medicine · 2017Article
- Article
- Novel immunotherapeutic approaches to the treatment of urothelial carcinoma.Therapeutic advances in urology · 2016Review
- Nonmuscle invasive bladder cancer: a primer on immunotherapy.Cancer biology & medicine · 2016Article
- Independent Replication of Published Germline Polymorphisms Associated with Urinary Bladder Cancer Prognosis and Treatment Response.Bladder cancer (Amsterdam, Netherlands) · 2016Article
- Dendritic Cell Activity Driven by Recombinant Mycobacterium bovis BCG Producing Human IL-18, in Healthy BCG Vaccinated Adults.Journal of immunology research · 2015Article
- Evolving immunotherapy strategies in urothelial cancer.American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin-18 (IL-18) has been demonstrated to synergize with BCG for induction of a T-helper-type 1 (Th1) immune response. Since successful treatment of superficial bladder cancer with BCG requires proper induction of Th1 immunity, we have developed a recombinant (r) BCG strain that functionally secretes mouse (m) IL-18. This rBCG-mIL-18 strain significantly increased production of the major Th1 cytokine IFN-gamma in splenocyte cultures, at levels comparable to that elicited by control BCG plus exogenous rIL-18. IFN-gamma production by splenocytes was eliminated by addition of neutralizing anti-IL-18 antibody. Endogenous IL-12 played a favourable role whereas IL-10 played an adverse role in rBCG-mIL-18-induced IFN-gamma production. Enhanced host antimycobacterial immunity was observed in mice infected with rBCG-mIL-18 which showed less splenic enlargement and reduced bacterial load compared to control mice infected with BCG. Further, splenocytes from rBCG-mIL-18-infected mice, in response to BCG antigen, displayed increased production of IFN-gamma and GMCSF, decreased production of IL-10, elevated cellular proliferation and higher differentiation of IFN-gamma-secreting cells. rBCG-mIL-18 also enhanced BCG-induced macrophage cytotoxicity against bladder cancer MBT-2 cells in a dose-dependent manner. Neutralizing all endogenous macrophage-derived cytokines tested (IL-12, IL-18 and TNF-alpha) as well as IFN-gamma severely diminished the rBCG-mIL-18-induced macrophage cytolytic activity, indicating a critical role for these cytokines in this process. Cytokine analysis for supernatants of macrophage-BCG mixture cultures manifested higher levels of IFN-gamma and TNF-alpha in rBCG-mIL-18 cultures than in control BCG cultures. Taken together, this rBCG-mIL-18 strain augments BCG's immunostimulatory property and may serve as a better agent for bladder cancer immunotherapy and antimycobacterial immunization.
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