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Inhibitory Effects of a Reengineered Anthrax Toxin on Canine Oral Mucosal Melanomas
Adriana Tomoko Nishiya1, Marcia Kazumi Nagamine1, Ivone Izabel Mackowiak da Fonseca1
1Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, SP, Brazil.
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.
Insights
A reengineered anthrax toxin shows promise for treating canine oral mucosal melanomas (OMM). Intratumoral injections reduced tumor bleeding and caused cell death, with no significant side effects observed in dogs with OMM.
Area of Science:
- Veterinary Oncology
- Molecular Biology
- Toxicology
Background:
- Canine oral mucosal melanomas (OMM) are common and have limited treatment options.
- Reengineered anthrax toxin targets tumor cells expressing urokinase plasminogen activator (uPA) and metalloproteinases (MMP-2).
- Previous studies demonstrated the toxin's antineoplastic effects in vitro and in vivo.
Purpose of the Study:
- To evaluate the efficacy of a reengineered anthrax toxin in treating canine OMM.
- To assess tumor response and potential side effects of the toxin therapy.
Main Methods:
- Immunohistochemistry was used to analyze OMM tissue for uPA, uPA receptor, MMP-2, MT1-MMP, and TIMP-2 expression.
- Five dogs with OMM received intratumoral injections of the reengineered anthrax toxin before surgical excision.
- Tumor response was evaluated using canine Response Evaluation Criteria in Solid Tumors (cRECIST).
Main Results:
- All OMM samples tested positive for the targeted biomarkers.
- All treated dogs achieved stable disease (cRECIST), with reduced tumor bleeding.
- Histopathology revealed tumor cell and blood vessel wall necrosis post-treatment.
- No significant systemic adverse events were observed.
Conclusions:
- The reengineered anthrax toxin demonstrated inhibitory effects on canine OMM when administered intratumorally.
- Systemic administration of this toxin represents a promising therapeutic strategy for canine OMM.
