2019 Funded Projects
For the 2019 the Canine Research Foundation funded 4 research projects.
Congratulations ot the following research teams
(1) Proteasome inhibitors for canine osteosarcoma: modelling efficacy in mice
(Dr Christine Hawkins, La Trobe University)
The bone cancer osteosarcoma is the fourth most common malignancy in pedigree dogs. It develops particularly frequently in large breeds: estimates of its incidence in Greyhounds, Rottweilers and Great Danes range from 5-13%. The highly malignant behaviour of osteosarcomas leads to an average postdiagnosis survival of only 3-4 months if untreated. Surgery and chemotherapy typically extend survival by less than a year and only 15% of optimally-treated canine osteosarcoma patients survive for more than 3 years.
To identify treatments that may more effectively treat this cancer, we tested a panel of recently-developed anti-cancer drugs for the ability to kill canine osteosarcoma cells in the laboratory. We found that levels of bortezomib (a drug that inhibits recycling of defective and surplus proteins within cells) that would be achievable in the bones and lungs of dogs, potently destroyed these cancer cells (Patasos, Shekhar & Hawkins, Vet Comp Oncol, accepted 29/5/18).
This study will build upon these exciting results to test whether bortezomib or other drugs that work via similar mechanisms can impede the growth of canine osteosarcomas implanted into mice. Promising results from this study would facilitate the design of clinical trials to evaluate these drugs in canine osteosarcoma patients, with the ultimate goal of enhancing survival of dogs diagnosed with this lethal cancer.
(2) Nasal microbiota in shelter dogs and carriage of Staphylococcus spp.
(Dr Justine Gibson, University of Queensland)
Staphylococcus pseudintermedius is a bacteria which is present on the skin and nostrils of healthy dogs as part of normal flora; however, it can cause a wide range of opportunistic infections involving the skin, ears, urinary tract, bone and surgical sites. Methicillin resistant S. pseudintermedius are resistant to all β-lactam antimicrobials such as penicillins and cephalosporins, can become multidrug resistant, have been shown to spread within veterinary environments and have the potential to infect people. Dogs which carry methicillin resistant or sensitive S. pseudintermedius are most at risk of infections. This study aims to use cutting-edge molecular microbiology technologies to profile the microbial diversity and abundance of nasal microbiota in dogs from a shelter and correlate this to carriage of methicillin resistant and sensitive S. pseudintermedius in dogs and the environment. For the first time, the associations between the resident nasal microbiota of dogs and how this dynamic population may prevent or favour the establishment of methicillin resistant and sensitive S. pseudintermedius will be investigated. The protective role(s) of the resident nasal microbiota can be explored to help encourage development of antimicrobial therapy or techniques which can maintain or restore indigenous microbiota, such as probiotics, to decrease the carriage of methicillin resistant and sensitive S. pseudintermedius in the canine population. If carriage of S. pseudintermedius can be decreased, canine infections, environmental spread and transmission of the organism to people and other animals can also be reduced.
(3) Bioprinted tissue constructs as a potential canine diabetes mellitus treatment
(Assoc Prof Paul Sheehy, University of Sydney)
Diabetes mellitus (insulin dependent or type 1) is a disease where the secretion of insulin from the pancreas is impaired leading to disruptions in normal metabolic regulation. If untreated, can lead to large changes in blood glucose concentration potentially resulting in coma and death. This disease affects approximately 0.5-1 % of dogs but may be higher is some breeds due to genetic factors. While dogs with this disease can lead relatively healthy lives, the ongoing administration of insulin can be challenging for owners and secondary conditions (eg cataracts) can develop if the management of the condition is less than optimal. An alternative approach utilised in humans is the transplantation of insulin producing cells from donors although this is less practical in dogs due to lack of donor tissues and the requirement for surgical implantation. 3 Dimensional Tissue Bioprinting is a contemporary tissue engineering strategy that is capable of generating implantable tissue constructs from cells and gel like materials, and may be capable of restoring tissue function impaired by degenerative disease or trauma. Within the context of canine diabetes mellitus, this technique could be utilised to build tissues containing insulin secreting cells to be used as a therapeutic construct implanted to function in place of the damaged pancreas. We have already initiated research to bioprint tissue constructs incorporating insulin secreting cells and this project is aimed to progress that research towards an implantable construct that may alleviate the impaired metabolic function in dogs suffering from canine diabetes mellitus.
(4) Development of chimeric antigen receptor T cells for dogs
(Dr Peter Bennett, University of Sydney)
Canine lymphoma is a relatively common cancer in dogs affecting about 30 dogs per 100,000 at risk. Current therapies are good at controlling the disease, but cure rates are less than 10%. Non-Hodgkin’s lymphoma in humans shares many characteristics with canine lymphoma but has a cure rate of over 60%. One recent development in treatment of lymphoma is the use of Chimeric Antigen Receptor T cells (CAR T cells). These are immune cells that are genetically engineered to express a special antibody-based receptor on their surface which enables them to see and kill cancer cells. The group has had antibody producing hybridomas made that target a common marker on the surface of lymphoma cells (CD22). To progress this work, cell lines need to be developed that express the canine CD22 to be able to select what appears to be the best antibody. Concurrently a canine B cell lymphoma cell line will be developed. Both will then be tested with CAR T cells that target canine CD22 to show binding accuracy and effective cell killing. These steps are required prior to developing cells from patients and testing them for safety and efficacy. This therapy when used in conjunction with chemotherapy has the potential to greatly improve the outcome for dogs without a major increase in risk of side effects
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Contact Details
Secretary: L Brodie Liaison Officer:Melbourne, VIC, Australia
Email : [email protected]