Naturally occurring cancers in pet dogs as pre-clinical models for cancer immunotherapy
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Despite the significant progress in tumor prevention, early detection, diagnosis and treatment made over recent decades, cancer is still an enormous public health challenge all around the world, with the number of people affected increasing every year. A great deal of effort is therefore being devoted to the search for novel safe, effective and economically sustainable treatments for the growing population of neoplastic patients. One main obstacle to this process is the extremely low percentage of therapeutic approaches that, after successfully passing pre-clinical testing, actually demonstrate activity when finally tested in humans. This disappointing and expensive failure rate is partly due to the pre-clinical murine models used for in vivo testing, which cannot faithfully recapitulate the multifaceted nature and evolution of human malignancies. These features are better mirrored in natural disease models, i.e., companion animals affected by cancers. Herein, we discuss the relevance of spontaneous canine tumors for the evaluation of the safety and anti-tumor activity of novel therapeutic strategies before in-human trials, and present our experience in the development of a vaccine that targets chondroitin sulphate proteoglycan (CSPG)4 as an example of these comparative oncology studies.
KeywordsComparative oncology CSPG4 DNA vaccination Melanoma Osteosarcoma PIVAC 18
Bruton’s tyrosine kinase
Genetically engineered T cells with chimeric antigen receptors
Cancer stem cells
Chondroitin sulphate proteoglycan 4
Comparative Oncology Trials Consortium
Cytotoxic T lymphocyte antigen-4
Focal adhesion kinase
Food and Drug Administration
Liposomal muramyl tripeptide phosphatidyl ethanolamine
National Cancer Institute
Programmed cell death receptor-1
Triple wild type
United States Department of Agriculture
Monoclonal antibodies directed towards different epitopes of the CSPG4 antigen (225.2, TP32, TP49 and VF20-VT87.41) used to perform flow cytometry analysis were kindly provided by Prof. Soldano Ferrone (Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA). We thank Dr. Dale Lawson for his revision and editing of the manuscript.
LT, GB, SI, DG and FR produced the results discussed in this review. FR, LT and GB performed mouse experiments and flow cytometry analysis, supervised by FC. SI and DG, under the supervision of PB, collaborated to produce the results in canine patients. FC, FR and LT provided major contributions in writing and discussing the manuscript. FC and EQ critically revised the manuscript. All authors read and approved the final version of the manuscript.
This work was supported by Grants from Fondazione Ricerca Molinette Onlus, the University of Turin (ex 60% 2018, intramural funds) and the Italian Ministry of Health (Progetti ordinari di Ricerca Finalizzata, RF-2013-02359216). FR was supported by a fellowship from Fondazione Italiana per la Ricerca sul Cancro (FIRC).
Compliance with ethical standards
Conflict of interest
The authors declare that no potential conflicts of interest exist.
Ethical approval and ethical standards
All the in vivo experiments were approved by the Italian Ministry of Health, authorization numbers 0006939-P-18/03/2015 (164/2015-PR) and 0004230-20/02/2018-DGSAF-MDS-P.
Mice used for the vaccination experiments reported in this paper were purchased from Charles River Laboratories or bred at the Molecular Biotechnology Center, University of Turin, where all mice were maintained and treated in accordance with University Ethical Committee and European Union guidelines under Directive 2010/63. The canine patients that were enrolled in veterinary trials were client-owned dogs, whose institutes of reference were the Veterinary Teaching Hospital of the University of Turin and the Veterinary clinics of South Rome, Italy. Dogs were treated according to the Good Clinical Practice guidelines for animal clinical studies, and rules imposed by the Ethical Committee of the University of Turin (Italy).
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