Dogs are man’s best friend and it is always distressing for dog owners when their beloved pets contract terminal illnesses. Canine cancer is the leading cause of death in dogs and when diagnosed with a terminal or terminal illness, there are often no treatment options available. In a recent study, however, a new form of chemoimmunotherapy was shown to be a promising treatment for altering the life course of dogs.
Scientists from the Translational Research Program (TRP) of the NUS Center for Cancer Research (N2CR) at the Yong Loo Lin School of Medicine at the National University of Singapore (NUS Medicine) used precision stem cell engineering technology to treat canines with cancer. In the study led by Associate Professor Too Heng-Phon of N2CR TRP and NUS Medicine’s Department of Biochemistry, the team engineered mesenchymal stem cells (MSCs), which are capable of seeking out cancerous tumours. These modified cells carry a powerful “kill-switch” (cytosine deaminase) that produces a high, localized concentration of a cancer-killing drug (5-fluorouracil) in the tumor environment and then induces anti-cancer immunity. Developing this therapy to treat canine patients is leading the team towards a better understanding of cancer treatments, as well as its use in human patients, as helping dogs with natural cancers provides valuable clues about human cancers .
Professor Assoc Too said: “To reuse stem cells for the treatment of cancer, it is usual to use viruses to introduce therapeutic genes into the cells. We have, however, designed a non-viral gene delivery platform that introduces a high payload of therapeutic genes into the stem cells, to effectively destroy cancer cells growing out of control. With this therapy which has been shown to be safe and which has demonstrated promising clinical benefits in animal patients, we hope to develop effective treatment options to help human cancer patients as well, which can improve their health without compromising their quality of life.”
Application of technology on canine cancer patients
The technology developed by the NUS Medicine team was first applied to canine patients in Singapore in 2018, in collaboration with Dr. Jean Paul Ly, CEO and Founder of Animal Wellness. The research team then collaborated with other veterinary partners and institutions, administered the therapy to a total of 65 dogs, as well as two cats, with conditions such as perianal adenoma, lung metastases and a sarcoma. Patients first received the precision MSCs by direct injections at the tumor site or through the bloodstream, followed by ingestion of oral pills containing a drug commonly used to treat fungal infections (5-flucytosine), for a few days. After one week, the cycle was repeated for two more weeks before the first treatment cycle was completed. The team then monitored the condition of the patients and repeated the course if necessary.
Among the animal patients who received the treatment for a period ranging from three to eight weeks, 56 showed signs of a positive response, of which 14 showed complete recovery from the treatment. Two animal patients remain cancer-free at least 30 months after treatment, while 46 patients showed good quality of life for two to 32 months with treatment. During the treatment of all the animal patients involved in the study, no significant side effects were observed – probably due to the localized presence of the therapeutic cells which remain in the tumor environment.
Despite significant advances in human cancer treatments, there is a considerable lag in the development of oncology therapies for animal patients comparatively. Until 2009, all animals were treated with generic human chemotherapy drugs on an off-label basis because there were no animal-specific cancer agents approved by the United States Food and Drug Administration (FDA) . Dr Lee Yee Lin, Founder and Chief Veterinarian, Gentle Oak Veterinary Clinic in Singapore, with whom the research team collaborated and is one of the study authors, said: “Therapies and advances in Allopathic medicine are usually developed primarily for humans before they However, in the trials of this study, dogs with cancer without any other viable treatment options are the main beneficiaries of the therapy – and many between them showed promising results with an improvement in their quality of life. Hopefully the therapy can become one of the standard options available to dogs in the near future, so that more patients can benefit from it.”
One of the team’s collaborative partners, Associate Professor Antonio Giuliano, Department of Veterinary Clinical Sciences, City University of Hong Kong, will also integrate the therapy into animal clinical studies in 2023.
To provide therapy as an accessible and affordable option for human patients
Stem cell modification therapy differs from other cell and gene therapies that use viruses to introduce genes into cells. Instead of using a virus, the modification involves the use of a chemical carrier, which is safer and faces fewer regulatory restrictions in treatment development. Compared to other cell and gene therapies, the therapy design has a much shorter cycle time and much lower production costs, paving the way for a more accessible and affordable option for cancer patients in the future. coming.
Dr. Ho Yoon Khei, Principal Investigator, N2CR TRP and Department of Biochemistry at NUS Medicine, and first author and lead scientist of the study, said: “Currently, we can develop this therapy for up to 18 human patients each week. . Beyond the results that have proven beneficial to our pets, we hope to expand the therapy to human patients in the future and improve healthcare outcomes for those with cancer, especially when they are not have more treatment options.
The research team is working with local and global health institutions to review the safety and efficacy of the therapy for veterinary medicine and discuss plans for clinical trials in human patients in Singapore and the Asia- Peaceful. These should begin in 2024.
Professor Chong Yap Seng, Lien Ying Chow Professor of Medicine, Dean of NUS Medicine, added: “Our research work at NUS Medicine aims to create real and significant health benefits for the populations we serve and ultimately to achieve better health care outcomes for all. We believe that this therapy developed by the N2CR will have a major impact on the health and well-being of patients with solid tumors and terminal cancers.”
The N2CR is one of NUS Medicine’s 10 Translational Research Programs (TRPs) aimed at creating a strong and cohesive scientific foundation to deliver impactful and meaningful research outcomes for the Singapore school and health system. Other areas besides cancer are cardiovascular disease, digital medicine, healthy longevity, human potential, immunology, infectious disease, precision medicine, synthetic biology, and nanomedicine. These 10 key focus areas, which are multidisciplinary and focused on health and disease, will create greater synergies and collaborations between basic scientists and clinician-scientists, strengthen programmatic research and provide research results to solve the clinically relevant problems and applications that are aligned with national standards. priorities.