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

Abstract

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.

The innate immune stimulant Amplimune® is safe to administer to young feedlot cattle

“…Amplimune also induced increases in total WBC count in heifers when administered via SC or IM injection at a dose rate of 2 mL; and increases in lymphocyte counts in heifers when administered via SC or IM injection at a dose rate of 5 mL. In other studies investigating MCWF, from non‐Amplimune sources, in mice, 47 dogs 48 and horses, 49 changes have been observed in a variety of parameters. Activation of cytotoxic T‐cells by MCWF induced the reduction of three different cancer cell lines in mice tumours 47 ; clinical symptoms of bladder cancer, including dysuria, pollakiuria and haematuria, were reduced following administration of MCWF in dogs 48 ; and a reduction in the number of mares positive for endometritis, based on exfoliative cytology and bacteriology, when administered MCWF at 48 h post‐experimental challenge 49 .…”

“…In other studies investigating MCWF, from non-Amplimune sources, in mice, 47 dogs 48 and horses, 49 changes have been observed in a variety of parameters. Activation of cytotoxic T-cells by MCWF induced the reduction of three different cancer cell lines in mice tumours 47 ; clinical symptoms of bladder cancer, including dysuria, pollakiuria and haematuria, were reduced following administration of MCWF in dogs 48 ; and a reduction in the number of mares positive for endometritis, based on exfoliative cytology and bacteriology, when administered MCWF at 48 h postexperimental challenge. 49 In these studies, immune activation was induced without excessive inflammation.…”

“…Other studies with different MCWFs have found increased production of a range of pro‐inflammatory cytokines including interleukin‐12 (IL‐12), interleukin‐6 (IL‐6), tumour necrosis factor‐alpha (TNFα) and interferon‐gamma (IFNγ), as well as increased neutrophils and primed macrophages in response to treatment 54,55 . The efficacy of MCWF from M. phlei to prevent and treat disease has also been investigated in horses and dogs 48,49 …”

“…54,55 The efficacy of MCWF from M. phlei to prevent and treat disease has also been investigated in horses and dogs. 48,49 Importantly, studies have also shown that treatment of cattle with M. phlei does not cause false-positive results in bovine tuberculosis and Johne's disease tests, making it safe for use in food-producing animals, without compromising disease surveillance. 51 Results of the current study suggest that Amplimune is safe to use in young beef cattle.…”

Effect of a Non-Specific Immune Stimulant (Amplimune™) on the Health and Production of Light Feedlot Calves

“…MCWF also has potential for use in other veterinary applications, such as the treatment of infectious diseases [11][12][13] and the treatment of cancer. 10,14 The mode of action of MCWF is based on the activation of innate and adaptive immunity 15 with the purpose of the recognition of, reaction to, and quick recovery from infections. 10,11,13 Previous studies have demonstrated that subcutaneous administration of MCWF in day-old calves resulted in decreased morbidity, decreased treatment costs and increased average daily gain.…”