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Article

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

by
Adriana Tomoko Nishiya
1,
Marcia Kazumi Nagamine
1,
Ivone Izabel Mackowiak da Fonseca
1,
Andrea Caringi Miraldo
1,
Nayra Villar Scattone
1,
José Luiz Guerra
1,
José Guilherme Xavier
2,
Mário Santos
2,
Cristina Oliveira Massoco de Salles Gomes
1,
Jerrold Michael Ward
3,
Shihui Liu
4,
Stephen Howard Leppla
5,
Thomas Henrik Bugge
6 and
Maria Lucia Zaidan Dagli
1,*
1
Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, SP, Brazil
2
Rous Animal Pathology, Private Veterinary Pathology Services. Av. Lacerda Franco 127, Sao Paulo 01536-000, SP, Brazil
3
Global Vet Pathology, Montgomery Village, MD 20886, USA
4
Aging Institute and Division of Infectious Diseases, Department of Medicine, University of Pittsburg, Pittsburgh, PA 15261, USA
5
Microbial Pathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
6
Proteases & Tissue Remodeling Section, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892, USA
*
Author to whom correspondence should be addressed.
Toxins 2020, 12(3), 157; https://doi.org/10.3390/toxins12030157
Submission received: 16 January 2020 / Revised: 20 February 2020 / Accepted: 20 February 2020 / Published: 2 March 2020
(This article belongs to the Section Bacterial Toxins)
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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.
Keywords: toxin; oral melanoma; dog; Bacillus anthracis; anthrax toxin; oral melanoma; dog; Bacillus anthracis; anthrax

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MDPI and ACS Style

Nishiya, A.T.; Nagamine, M.K.; Fonseca, I.I.M.d.; Miraldo, A.C.; Villar Scattone, N.; Guerra, J.L.; Xavier, J.G.; Santos, M.; Massoco de Salles Gomes, C.O.; Ward, J.M.; et al. Inhibitory Effects of a Reengineered Anthrax Toxin on Canine Oral Mucosal Melanomas. Toxins 2020, 12, 157. https://doi.org/10.3390/toxins12030157

AMA Style

Nishiya AT, Nagamine MK, Fonseca IIMd, Miraldo AC, Villar Scattone N, Guerra JL, Xavier JG, Santos M, Massoco de Salles Gomes CO, Ward JM, et al. Inhibitory Effects of a Reengineered Anthrax Toxin on Canine Oral Mucosal Melanomas. Toxins. 2020; 12(3):157. https://doi.org/10.3390/toxins12030157

Chicago/Turabian Style

Nishiya, Adriana Tomoko, Marcia Kazumi Nagamine, Ivone Izabel Mackowiak da Fonseca, Andrea Caringi Miraldo, Nayra Villar Scattone, José Luiz Guerra, José Guilherme Xavier, Mário Santos, Cristina Oliveira Massoco de Salles Gomes, Jerrold Michael Ward, and et al. 2020. "Inhibitory Effects of a Reengineered Anthrax Toxin on Canine Oral Mucosal Melanomas" Toxins 12, no. 3: 157. https://doi.org/10.3390/toxins12030157

APA Style

Nishiya, A. T., Nagamine, M. K., Fonseca, I. I. M. d., Miraldo, A. C., Villar Scattone, N., Guerra, J. L., Xavier, J. G., Santos, M., Massoco de Salles Gomes, C. O., Ward, J. M., Liu, S., Leppla, S. H., Bugge, T. H., & Dagli, M. L. Z. (2020). Inhibitory Effects of a Reengineered Anthrax Toxin on Canine Oral Mucosal Melanomas. Toxins, 12(3), 157. https://doi.org/10.3390/toxins12030157

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