Th1 Cytokine-Secreting Recombinant Bacillus Calmette-Guérin: Prospective Use in Immunotherapy of Bladder Cancer

Luo, Yi; Henning, Jonathan R.; O’Donnell, Michael A.

doi:10.5772/22142

Cited by 16 publications

(20 citation statements)

References 128 publications

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“…Increased levels of cytokines in the serum of patients who received CIK cell infusion suggests the presence of CIK cell-induced T helper 1 (Th1) cell responses. Since Th1 responses seem to be essential in cancer immunotherapy (62,63), this may indicate a therapeutic potential of CIK cell therapy. It was not possible to determine how Tregs and TGF-β interact with each other in the blood from the current results.…”

Section: Discussionmentioning

confidence: 99%

Cytokine-induced killer cell therapy for modulating regulatory T cells in patients with non-small cell lung cancer

Wang

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Previous studies have reported that regulatory T cells (Tregs), which are physiologically engaged in the maintenance of immunological self-tolerance, have a critical role in the regulation of the antitumor immune response. Targeting Tregs has the potential to augment cancer vaccine approaches. The current study therefore aimed to evaluate the role of cytokine-induced killer (CIK) cell infusion in modulating Tregs in patients with non-small cell lung cancer (NSCLC). A total of 15 patients with advanced NSCLC were treated by an infusion of CIK cells derived from autologous peripheral blood mononuclear cells (PBMCs). By using flow cytometry and liquid chip analysis, subsets of T cells and natural killer (NK) cells in peripheral blood, and plasma cytokine profiles in the treated patients, were analyzed at 2 and 4 weeks after CIK cell infusion. Cytotoxicity of PBMCs (n=15) and NK cells (n=6) isolated from NSCLC patients was evaluated before and after CIK cell therapy. Progression-free survival (PFS) and overall survival (OS) were also assessed. Analysis of the immune cell populations before and after treatment showed a significant increase in NK cells (P<0.05) concomitant with a significant decrease in Tregs (P<0.01) at 2 weeks post-infusion of CIK cells compared with the baseline. NK group 2D receptor (NKG2D) expression on NK cells was also significantly increased at 2 weeks post-infusion compared with the baseline (P<0.05). There was a positive correlation between NKG2D expression and the infusion number of CIK cells (P<0.05).

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Section: Discussionmentioning

confidence: 99%

Cytokine-induced killer cell therapy for modulating regulatory T cells in patients with non-small cell lung cancer

Wang

et al. 2017

Experimental and Therapeutic Medicine

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“…One approach is the generation of Th1 cytokine‐expressing recombinant forms of BCG (rBCG). In animal models, some cytokine‐expressing rBCGs showed promising results against malignant melanoma and breast cancer; however, studies using intravesical models of bladder cancer are still limited …”

Section: Prospect Of Engineered Mycobacterium Vaccinementioning

confidence: 99%

Bacillus Calmette–Guerin (BCG) immunotherapy for bladder cancer: Current understanding and perspectives on engineered BCG vaccine

et al. 2013

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Since the first report in 1976, accumulated clinical evidence has supported intravesical Bacillus Calmette-Guerin (BCG) therapy as one of the standard methods of management of intermediateand high-risk non-muscle invasive bladder cancer. Despite its efficacy, intravesical BCG therapy is associated with a variety of adverse events (AEs), most of which are tolerable or controllable with supportive care. However, some patients receiving intravesical BCG therapy may experience uncommon but severe AEs, leading to cessation of BCG therapy. Not all, but most severe AEs result from either local or systemic infection with live BCG. Intravesical instillation of BCG elicits multiple immune reactions, although the precise immunological mechanism of BCG therapy is not clear. It is convenient to separate the complex reactions into the following three categories: infection of urothelial cells or bladder cancer cells, induction of immune reactions, and induction of antitumor effects. Recently, our knowledge about each category has increased. Based on this understanding, predictors of the efficacy of intravesical BCG therapy, such as urinary cytokine measurement and cytokine gene polymorphism, have been investigated. Recently, preclinical studies using a novel engineered mycobacterium vaccine have been conducted to overcome the limitations of BCG therapy. One approach is Th1 cytokineexpressing recombinant forms of BCG; another approach is development of non-live bacterial agents to avoid AEs due to live BCG infection. We also briefly describe our approach using an octaarginine-modified liposome-incorporating BCG cell wall component to develop future substitutes for live BCG. (Cancer Sci 2013; 104: 22-27) I ntravesical Bacillus Calmette-Guerin (BCG) therapy is undoubtedly the most successful immunotherapy for cancer.(1) In 1976, Morales et al.(2) reported the prophylactic effect of topical application of live BCG to the bladder to prevent bladder cancer recurrence. In the original protocol, 120 mg BCG diluted with 50 mL saline was instilled into the bladder via a urethral catheter with an indwelling time of 2 h and was repeated once a week for 6 weeks. Since then, intravesical BCG therapy has been widely used and is recognized as a standard method of management of intermediate-and high-risk non-muscle invasive bladder cancer, although the optimal schedule and duration are still being tested. Despite its efficacy, intravesical BCG therapy is not free from severe and possibly fatal complications due to the use of live BCG. However, the precise immunological mechanism of BCG therapy is not clear, and understanding the immune responses induced by BCG is needed to develop a more active and less toxic immunotherapy. In this review, we summarize basic and clinical information about intravesical BCG therapy, and also describe the prospect of an engineered mycobacterium vaccine. Current clinical use of intravesical BCG therapyAt initial diagnosis, approximately 70% of bladder cancer patients are diagnosed with non-muscle invasive blad...

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“…In vitro and in vivo studies demonstrated that an effective immunotherapeutic treatment should activate antigen-presenting cells and strongly induce Th-121,28,29 . Thus, if proper primary induction is achieved with viable mycobacteria, nonviable mycobacteria will probably produce an effective recall response.…”

mentioning

confidence: 99%

γ Irradiated Mycobacteria Enhance Survival in Bladder Tumor Bearing Mice Although Less Efficaciously than Live Mycobacteria

et al. 2016

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Th1 Cytokine-Secreting Recombinant Bacillus Calmette-Guérin: Prospective Use in Immunotherapy of Bladder Cancer

Cited by 16 publications

References 128 publications

Cytokine-induced killer cell therapy for modulating regulatory T cells in patients with non-small cell lung cancer

Cytokine-induced killer cell therapy for modulating regulatory T cells in patients with non-small cell lung cancer

Bacillus Calmette–Guerin (BCG) immunotherapy for bladder cancer: Current understanding and perspectives on engineered BCG vaccine

γ Irradiated Mycobacteria Enhance Survival in Bladder Tumor Bearing Mice Although Less Efficaciously than Live Mycobacteria

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