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Updated: May 3, 2026
Production and Purification of Non Replicative Canine Adenovirus Type 2 Derived Vectors
Published on: December 3, 2013
A pRb-responsive, RGD-modified, and hyaluronidase-armed canine oncolytic adenovirus for application in veterinary
Eduardo Laborda1, Cristina Puig-Saus2, Alba Rodriguez-García2
11] Translational Research Laboratory, IDIBELL-Institut Català d'Oncologia, Barcelona, Spain [2] Biochemistry and Molecular Biology Department, Autonomous University of Barcelona, Barcelona, Spain.
Abstract:
Human and canine cancer share similarities such as genetic and molecular aspects, biological complexity, tumor epidemiology, and targeted therapeutic treatment. Lack of good animal models for human adenovirotherapy has spurred the use of canine adenovirus 2-based oncolytic viruses. We have constructed a canine oncolytic virus that mimics the characteristics of our previously published human adenovirus ICOVIR17: expression of E1a controlled by E2F sites, deletion of the pRb-binding site of E1a, insertion of an RGD integrin-binding motif at the fiber Knob, and expression of hyaluronidase under the major late promoter/IIIa protein splicing acceptor control. Preclinical studies showed selectivity, increased cytotoxicity, and strong hyaluronidase activity. Intratumoral treatment of canine osteosarcoma and melanoma xenografts in mice resulted in inhibition of tumor growth and prolonged survival. Moreover, we treated six dogs with different tumor types, including one adenoma, two osteosarcomas, one mastocitoma, one fibrosarcoma, and one neuroendocrine hepatic carcinoma. No virus-associated adverse effects were observed, but toxicity associated to tumor lysis, including disseminated intravascular coagulation and systemic failure, was found in one case. Two partial responses and two stable diseases warrant additional clinical testing.
Insights
This study developed a canine oncolytic virus for cancer therapy, showing promising preclinical results in inhibiting tumor growth and prolonging survival in animal models. Clinical trials in dogs demonstrated safety and efficacy, warranting further investigation.
Area of Science:
- Veterinary Medicine
- Oncology
- Virology
Background:
- Human and canine cancers exhibit shared genetic, molecular, and epidemiological characteristics.
- Canine adenovirus 2 serves as a valuable model for human adenovirotherapy due to similarities in cancer biology.
- Limitations in existing animal models necessitate the development of effective oncolytic viruses for comparative oncology.
Purpose of the Study:
- To construct and evaluate a novel canine oncolytic virus (COV) based on human adenovirus ICOVIR17.
- To assess the preclinical efficacy and safety of the COV in canine cancer models.
- To investigate the therapeutic potential of COV in naturally occurring canine tumors.
Main Methods:
- Engineered a COV with specific modifications: E1a expression controlled by E2F sites, pRb-binding site deletion, RGD motif insertion, and hyaluronidase expression.
- Conducted preclinical studies using canine osteosarcoma and melanoma xenografts in mice.
- Administered intratumoral COV treatment to six dogs with various tumor types.
Main Results:
- Preclinical studies demonstrated COV's selectivity, enhanced cytotoxicity, and significant hyaluronidase activity.
- Intratumoral COV treatment in mice led to tumor growth inhibition and extended survival.
- In dogs, no virus-associated adverse effects were noted; however, one case experienced toxicity linked to tumor lysis. Two partial responses and two stable disease cases were observed.
Conclusions:
- The developed canine oncolytic virus exhibits promising preclinical anti-tumor activity and safety.
- Clinical evaluation in dogs suggests therapeutic potential, with partial responses and stable disease observed.
- Further clinical investigation is warranted to establish the efficacy of this COV in canine cancer patients.
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