Mycobacterial Cell Wall Extract for Treatment of Carcinoma in Situ of the Bladder

Morales, Álvaro; Chin, Joseph L.; Ramsey, Ernest W.

doi:10.1016/s0022-5347(05)65642-x

Cited by 62 publications

(27 citation statements)

References 33 publications

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“…The synthesis of signifi cant amounts of IL-12 and IL-18 following topical administration of MCWF is of particular interest since these cytokines are known to possess potent anti-cancer activity following systemic or local administration [32]. Clinical evaluation of MCWF, formulated as an oil in water emulsion in the treatment of human patients with CIS of the bladder, demonstrated anticancer activity in conjunction with a satisfactory safety profi le [16]. CWF was administered intravesically in humans using an MCWF emulsion formulation and resulted in recurrence-free survival rates of 62.5% at 12 weeks, 49.3% at 24 weeks, and 41.1% at 60 weeks [14].…”

Section: Discussionmentioning

confidence: 99%

“…Previous clinical experience with MCWF emulsion in humans showed clinical effectiveness in the treatment of patients with CIS of the bladder who were treatment naïve or in whom BCG treatment had failed [13,14,16]. The small pilot clinical study was designed to address the clinical safety and effectiveness of the same MCWF composition, formulated as an emulsion, for the treatment of TCC in dogs.…”

Section: Discussionmentioning

confidence: 99%

“…In the human oncology fi eld, recent interest has focused on the use of mycobacterium cell wall preparations to elicit clinical responses without a number of the undesirable side effects associated with the use of live Mycobacterium bovis strain Bacillus CalmetteGuérin (BCG) which is a standard treatment option for human bladder cancer [13][14][15][16][17]. Mycobacterium cell wall fraction (MCWF) is prepared from the non-pathogenic microorganism Mycobacterium phlei [18].…”

Section: Introductionmentioning

confidence: 99%

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The in Vitro and in Vivo Anti-Cancer Potential of Mycobacterium Cell Wall Fraction (MCWF) Against Canine Transitional Cell Carcinoma of the Urinary Bladder

Filion¹,

Rodrigues²,

Johannes

et al. 2017

Acta Veterinaria

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Transitional cell carcinoma (TCC), is the most common form of urinary bladder cancer in dogs and represents 2% of all reported canine cancers. Canine TCC is usually a high-grade invasive cancer and problems associated with TCC include urinary tract obstruction and distant metastases in more than 50% of affected dogs. TCC is most commonly located in the trigone region of the bladder precluding complete surgical resection. Current treatment options for TCC in dogs include medical therapy, surgery or radiation. Mycobacterium Cell Wall Fraction (MCWF) is a biological immunomodulator derived from non-pathogenic Mycobacterium phlei. MCWF possesses a potential in multiple veterinary areas such as anticancer therapy, palliative care and treatment of infectious diseases in both small and large animals. MCWF is considered a bifunctional anti-cancer agent that induces apoptosis of cancer cells and stimulates cytokine and chemokines synthesis by cells of the immune system. Here we report the results from in vitro and in vivo studies that could suggest use of MCWF as an additional treatment option for TCC in dogs. Particularly, we demonstrated that MCWF induces a concentration dependent inhibition of proliferation of K9TCC cells which was associated with the induction of apoptosis as measured by the proteolytic activation of caspase-3 and the degradation of PARP. Furthermore, we demonstrated the safety and potential for in vivo MCWF treatment effi cacy in dogs bearing stage T2 TCC by reducing clinical signs, and improving the quality of life in dogs with TCC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The in Vitro and in Vivo Anti-Cancer Potential of Mycobacterium Cell Wall Fraction (MCWF) Against Canine Transitional Cell Carcinoma of the Urinary Bladder

Filion¹,

Rodrigues²,

Johannes

et al. 2017

Acta Veterinaria

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“…In order to reduce the side effects of BCG and to improve efficacy, interesting approaches are developed, such as the application of a cell wall -DNA complex (MCC) of Mycobacterium phlei, which was effective in patients who failed BCG therapy (Morales et al, 2001), genetically engineered BCG secreting relevant cytokines such as human lL-2 (Yamada et al, 2000), or treatment schedules consisting of three times viable BCG and three subsequent instillations with killed BCG (De Boer et al, 2003).…”

mentioning

confidence: 99%

Role of urothelial cells in BCG immunotherapy for superficial bladder cancer

2004

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Intravesical instillation of Bacillus Calmette-Guérin (BCG) is used for the treatment of superficial bladder cancer, both to reduce the recurrence rate of bladder tumour and to diminish the risk of progression. Since its first therapeutic application in 1976, major research efforts have been directed to decipher the exact mechanism of action of the BCG-associated antitumour effect. Bacillus Calmette-Guérin causes an extensive local inflammatory reaction in the bladder wall. Of this, the massive appearance of cytokines in the urine of BCG-treated patients stands out. Activated lymphocytes and macrophages are the most likely sources of these cytokines, but at present other cellular sources such as urothelial tumour cells cannot be ruled out. Bacillus Calmette-Guérin is internalised and processed both by professional antigen-presenting cells and urothelial tumour cells, resulting in an altered gene expression of these cells that accumulates in the presentation of BCG antigens and secretion of particular cytokines.

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“…A subsequent Th1 cytokine polarized response is characterized by the production of elevated levels of interleukin-2 (IL-2), interleukin-12 (IL-12), interferon-gamma (IFN-g), and possibly a major histocompatibility complex (MHC) class I presentation of tumor rejection antigens on the urothelial cell surface to specific CD8 þ T lymphocytes. 5 Although there have been some reports of successful attempts to reduce adverse effects and increase efficacy using nonviable heat-inactivated BCG and BCG subfractions, 6,7 others have found this to be less effective than treatment with viable organisms. [8][9][10] Treatment failure was blamed on the lack of urothelial retention of these BCG products and inadequate delivery of the BCG components.…”

mentioning

confidence: 99%

Treatment of bladder carcinomas using recombinant BCG DNA vaccines and electroporative gene immunotherapy

et al. 2004

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Intravesical immunotherapy with live Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the treatment of choice for superficial bladder cancers. Nevertheless, a significant proportion of patients do not respond to this therapy, and adverse effects are common. Here, we report the cloning of recombinant mycobacterial DNA vaccines and demonstrate the ability of multicomponent and multisubunit DNA vaccines to enhance Th1-polarized cytokine-mediated responses as well as effector cell responses. Splenocytes from immunized groups of mice were restimulated in vitro and examined for cytotoxicity against murine bladder tumur (MBT-2) cells. We used four combined recombinant BCG DNA vaccines (poly-rBCG) for electroporative gene immunotherapy (EPGIT) in vivo, and found that tumor growth was significantly inhibited and mouse survival was prolonged. Increased immune cell infiltration and induction of apoptosis were noted after treatment with poly-rBCG alone, with the murine interleukin-12 (mIL-12) vaccine alone, and-most significantly-with the poly-rBCG þ mIL-12 vaccine combination. Electroporation of poly-rBCG þ mIL-12 resulted in complete tumor eradication in seven of eight mice (Po.01) within 28 days. Thus, EPGIT using multicomponent multisubunit BCG is highly effective in the treatment of bladder cancer. This approach presents new possibilities for the treatment of bladder cancer using recombinant BCG DNA vaccines.

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Mycobacterial Cell Wall Extract for Treatment of Carcinoma in Situ of the Bladder

Cited by 62 publications

References 33 publications

The in Vitro and in Vivo Anti-Cancer Potential of Mycobacterium Cell Wall Fraction (MCWF) Against Canine Transitional Cell Carcinoma of the Urinary Bladder

The in Vitro and in Vivo Anti-Cancer Potential of Mycobacterium Cell Wall Fraction (MCWF) Against Canine Transitional Cell Carcinoma of the Urinary Bladder

Role of urothelial cells in BCG immunotherapy for superficial bladder cancer

Treatment of bladder carcinomas using recombinant BCG DNA vaccines and electroporative gene immunotherapy

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