Abstract
Canine oral mucosal melanomas (OMM) are the most common oral malignancy in dogs and few treatments are available. Thus, new treatment modalities are needed for this disease. Bacillus anthracis (anthrax) toxin has been reengineered to target tumor cells that express urokinase plasminogen activator (uPA) and metalloproteinases (MMP-2), and has shown antineoplastic effects both, in vitro and in vivo. This study aimed to evaluate the effects of a reengineered anthrax toxin on canine OMM. Five dogs bearing OMM without lung metastasis were included in the clinical study. Tumor tissue was analyzed by immunohistochemistry for expression of uPA, uPA receptor, MMP-2, MT1-MMP and TIMP-2. Animals received either three or six intratumoral injections of the reengineered anthrax toxin prior to surgical tumor excision. OMM samples from the five dogs were positive for all antibodies. After intratumoral treatment, all dogs showed stable disease according to the canine Response Evaluation Criteria in Solid Tumors (cRECIST), and tumors had decreased bleeding. Histopathology has shown necrosis of tumor cells and blood vessel walls after treatment. No significant systemic side effects were noted. In conclusion, the reengineered anthrax toxin exerted inhibitory effects when administered intratumorally, and systemic administration of this toxin is a promising therapy for canine OMM.
Highlights
Oral mucosal melanomas (OMM) are the most common oral malignancy in dogs [1,2]
Five dogs with spontaneous oral mucosal melanomas (OMM) were included in the study and the dogs’
(dogs 1–4) and tumors were mostly located in the maxilla (3/5), followed by mandible (1/5), and hard palate (1/5)
Summary
Oral mucosal melanomas (OMM) are the most common oral malignancy in dogs [1,2]. OMM are characterized by local infiltration and metastasis to regional lymph nodes (11.4–53% of cases) [3,4]and lungs (23–27%). Oral mucosal melanomas (OMM) are the most common oral malignancy in dogs [1,2]. OMM are characterized by local infiltration and metastasis to regional lymph nodes (11.4–53% of cases) [3,4]. The common treatment modalities for OMM include surgery, radiation therapy, chemotherapy and immunotherapy [2]. Like vaccines, are commercially available and have some inhibitory effects [8,9]. Some new therapies, such as nanotechnology-based immunotherapy [10], electro-chemotherapy [11], and toceranib phosphate (Palladia® ), alone or in combination [12], have been reported, but only partial responses were observed.
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