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Inhibitory Effects of a Reengineered Anthrax Toxin on Canine Oral Mucosal Melanomas

2020; Multidisciplinary Digital Publishing Institute; Volume: 12; Issue: 3 Linguagem: Inglês

10.3390/toxins12030157

2072-6651

Adriana Tomoko Nishiya, Márcia Kazumi Nagamine, Ivone Izabel Mackowiak da Fonseca, Andrea Caringi Miraldo, Náyra Villar Scattone, José Luiz Guerra, José Guilherme Xavier, Mário Santos, Cristina Oliveira Massoco de Salles Gomes, Jerrold M. Ward, Shihui Liu, Stephen H. Leppla, Thomas Bugge, M.L. Dagli,

Rabies epidemiology and control

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.