Evaluation of Adverse Events in Dogs with Adenoviral Therapy by Intralymphonodal Administration in Canine Spontaneous Multicentric Lymphosarcoma

L. Núñez-Ochoa, V. Madrid-Marina and A. Gutiérrez-López

Department of Pathology, Faculty of Veterinary Medicine and Zootechnics, CDMX, Mexico
Direction of Molecular Virology, Infectious Diseases Research Center, National Institute of Public Health, CDMX Mexico
Cellular Therapy Unit, Rehabilitation National Institute, CDMX, Mexico. Current address: Oncolytics Biotech Inc.

^*Correspondance to: L. Núñez-Ochoa 

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Abstract:

Background: Therapy administration in cancer is mainly performed by intravenous, oral, and in situ routes. Adverse Events (AE) are a significant limitation of adenoviral vectors during somatic gene therapy. There are some partial evaluations of AE in canine cancer research. The objective of this study was to evaluate AE in adenoviral vector-mediated gene therapy administered by Intralymphonodal Route (ILNR) in canine lymphosarcoma.Methods: AE were determined in five dogs with spontaneous multicentric lymphosarcoma. A non replicative recombinant adenovirus vector with a LacZ reporter gene was administered once by ILNR at a starting dose of 1.35 X 10¹⁰ pfu/kg, with a dose-escalation model to 1.25 X 10¹² pfu/kg considered under these conditions, as the Maximum Tolerated Dose (MTD). AE was evaluated by a canine scale for attribution of AE based in selected clinical findings, hemogram, biochemistry, and urinalysis.
Results: No significant AE were observed during the study, therefore, no Dose-Limiting Toxicity (DLT) and MTD were found in any dog.Conclusion: Administration of adenovirus vector exhibited no clinical, nor laboratory significant AE in this canine ILNR clinical trial. This suggests that adenoviral gene therapy by ILNR is safe for use in dogs with lymphosarcoma and a potential model of administration in animals and human beings with metastasis to lymph nodes.

Keywords:

Adverse events; Dogs; Lymph node; Intralymphonodal administration; Adenoviral vector; Gene therapy; Lymphosarcoma; Lymphoma; Hemogram; Clinical biochemistry

Cite the Article:

Núñez-Ochoa L, Madrid-Marina V, Gutiérrez-López A. Evaluation of Adverse Events in Dogs with Adenoviral Therapy by Intralymphonodal Administration in Canine Spontaneous Multicentric Lymphosarcoma. Clin Oncol. 2017; 2: 1258.