Dogs are often considered a person's closest companion, and it can be heartbreaking for their owners when they fall ill with a terminal disease. Cancer is the number one cause of death in dogs, and unfortunately, when it is detected at a late stage, there are often no viable treatment options. A recent study has presented a new form of chemoimmunotherapy that holds much promise as a treatment and could change the fate of affected dogs.
Researchers at the National University of Singapore's Centre for Cancer Research utilized stem cell engineering technology to treat canine cancer in a study. The lead researcher, Associate Professor Too Heng-Phon, and his team modified Mesenchymal Stem Cells (MSCs) to target cancerous tumors by carrying a "kill-switch" called cytosine deaminase that generates a high concentration of the cancer-killing drug 5-fluorouracil in the tumor environment and triggers anti-cancer immunity.
This therapy has the potential to lead to a better understanding of cancer treatment and its application to human patients, as studying naturally occurring cancers in dogs provides valuable insights into human cancers. Associate Professor Too stated that to utilize stem cells for cancer therapy, it is common to introduce therapeutic genes using viruses. However, the team at NUS Medicine developed a non-viral gene delivery platform that effectively inserts a high amount of therapeutic genes into stem cells to eradicate the cancer cells that have grown out of control.
'Kill Switch' Therapy
The therapy has been proven safe and has shown promising results in animal patients, and the goal is to apply this to human cancer patients to provide effective treatment options that improve their health without negatively impacting their quality of life. In 2018, the team from NUS Medicine-first tested their technology on canine patients in Singapore in partnership with Dr. Jean Paul Ly, CEO and founder of Animal Wellness, as per ScienceDaily.
They then expanded their collaboration with veterinary partners and institutions, administering the therapy to 65 dogs and two cats suffering from conditions such as perianal adenoma, lung metastasis, and sarcoma. The treatment involved the injection of precision-engineered MSCs directly into the tumor site or through the bloodstream, followed by the consumption of oral pills containing the antifungal drug 5-flucytosine over several days. This process was repeated for two more weeks after the initial treatment before being monitored and repeated as necessary.
Of the animal patients that received the therapy, which lasted from three to eight weeks, 56 showed positive results, with 14 fully recovering. Two patients remained cancer-free at least 30 months after treatment, and 46 had improved quality of life between two to 32 months post-treatment. During the treatment, no significant side effects were observed in any patients, possibly due to the localized presence of the therapeutic cells within the tumor environment. Despite progress in human cancer treatments, there has been a significant delay in developing oncology therapies for animals.
Promising Treatment for Dog's Cancer
Before 2009, all animals were treated with generic human chemotherapy drugs, as the FDA approved no animal-specific anti-cancer drugs. Dr. Lee Yee Lin, who collaborated with the research team and is one of the study's authors, said that therapies and advancements in medicine are usually developed first for humans, then applied to animals. In this study, dogs with no other treatment options were the primary recipients of the therapy, and many showed promising results and improved quality of life. Dr. Lin hopes this therapy will soon become a standard option for dogs and that more patients can benefit from it.
The team working on the therapy has a new collaborator, Assoc Prof Antonio Giuliano, who will be conducting animal clinical studies with the therapy in 2023. Unlike other cell and gene therapies that use viruses to introduce genes, this therapy uses a chemical carrier, which is considered safer and faces fewer regulatory hurdles in its development. The therapy also has a shorter cycle and lower production cost compared to other cell and gene therapies, making it a more feasible and affordable option for cancer patients in the future.
Dr. Ho Yoon Khei, the senior research fellow of N2CR TRP and Department of Biochemistry at NUS Medicine, who was the first author and lead scientist of the study, expressed his hope to extend the therapy that has been developed to human patients who have cancer and have no treatment options left. The team can produce the therapy for up to 18 patients each week. The team is working with various health institutions in Singapore and the Asia Pacific region to assess the safety and efficacy of the therapy for veterinary medicine and to plan clinical trials for human patients, which are expected to start in 2024.
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