Scientists from the NUS Center for Cancer Research at the Yong Loo Lin College of Medicine of the National University of Singapore (NUS Medicine) have successfully used technology stem cell precision engineering to treat the dogs advanced-stage cancer patients, but could this technique be effective in human cancers?
As the researchers remember, the canine cancer is the leading cause of death in dogs And, when they are diagnosed with a terminal or advanced-stage disease, there are often no treatment options available. In the aforementioned study, however, a novel form of chemo-immunotherapy has shown promise as a life-altering treatment for dogs.
In it studydirected by associate professor Too Heng-Phon, from the TRP N2CR and the Department of Biochemistry at NUS Medicinethe team modified mesenchymal stem cells (MSCs), capable of searching for cancerous tumors. These modified cells carry a powerful “kill switch” (cytosine deaminase) producing a high and localized concentration of an anticancer drug (5-fluorouracilo) in the tumor environment and subsequently induces anticancer immunity.
The development of this therapy to treat canine patients leads the team towards a better understanding of cancer treatments, as well as their use in human patients, since helping dogs with naturally occurring cancers provides ‘valuable clues’ about human cancersaccording to the study.
“To reuse stem cells in cancer treatment, it is common to use viruses to deliver therapeutic genes into cells. However, we have designed a non-viral gene delivery platform that introduces a large number of therapeutic genes in stem cells to effectively destroy cancer cells growing out of control,” he says.
“Therapeutic genes in stem cells to effectively destroy out-of-control cancer cells”
“With this therapy, which has been shown to be safe and has shown promising clinical benefits in animal patientswe hope to develop effective treatment options to help human cancer patients as well, which can improve their health without compromising their quality of life,” the researchers write.
Application of technology in canine cancer patients
The technology developed by the NUS Medicine team was applied by first time in canine patients in Singapore in 2018, in a collaboration with Dr. Jean Paul Ly, CEO and Founder of Animal Wellness. Thereafter, the research team collaborated with more partners and veterinary institutions, administered the therapy to a total of 65 dogs, as well as two cats, with conditions such as perianal adenoma, lung metastasis, and sarcoma.
The patients first received the Precision Engineered CMM through direct injections into the tumor or through the bloodstreamfollowed by ingestion for a few days of oral pills containing a drug commonly used to treat fungal infections (5-flucytosine). After one week, the cycle was repeated for two more weeks before completing the first treatment cycle. The team then monitored the condition of the patients and repeated the cycle when necessary.
Among animal patients receiving treatment for a period of between three and eight weeks, 56 showed signs of positive response, 14 of whom fully recovered from treatment. Two animal patients remain cancer-free at least 30 months after treatment, while 46 patients showed good quality of life between two and 32 months with treatment. During the therapy of all the animals participating in the study, no significant side effects were observed, possibly 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 Huge delay in developing cancer therapies for animal patients compared. Until 2009, all animals were treated with off-label generic human chemotherapy drugs, as there were no US Food and Drug Administration (FDA)-approved animal-specific anticancer agents.
The doctor Lee Yee Lin, Founder and Chief Veterinarian at Gentle Oak Veterinary Clinic in Singapore, with whom the research team collaborated and one of the authors of the study, has clarified that therapies and advances in allopathic medicine are usually developed primarily for humans, before being applied to animals. “However, as part of the trials in this study, the main recipients of the therapy are dogs with cancer who have no other viable treatment options, and many of them have shown promising results with improved quality of life. Let’s hope that the therapy may become one of the standard options available to dogs in the near future, so that more patients can benefit from it,” he says.
“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.”
Offer the therapy as an 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 viruses, the modification involves the use of a chemical carrier, which is safer and faces fewer regulatory constraints on treatment development. Compared to other cell and gene therapies, the therapy design has a significantly shorter life cycle and much lower production costs, paving the way for a more accessible and affordable option for cancer patients in the future.
The doctor To Yoon Khei, principal investigator of the N2CR TRP and the Department of Biochemistry of NUS Medicineand first author and lead scientist of the study, has announced that it is currently possible to develop this therapy for up to 18 human patients each week. “Beyond the results that have been shown to benefit our companion animals, we are hopeful of extending the therapy to human patients in the future and improving healthcare outcomes for those with cancer, especially when they are left with no treatment options.” “, it states.
The research team is working with local and global healthcare institutions to review the safety and efficacy of the therapy in veterinary medicine and to discuss plans for clinical trials in human patients in Singapore and the Asia-Pacific region. They are expected to start in 2024.
“We believe that this N2CR-developed therapy will have a major impact on the health and well-being of patients with solid tumors and advanced-stage cancer.”
“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 advanced stage cancer“, specified the professor Chong Yap Seng, Lien Ying Chow Professor of Medicine and Dean of the NUS Faculty of Medicine. “Our research work at the NUS Faculty of Medicine aims to create real and significant health benefits for the populations we serve and ultimately improve health care outcomes for all,” he concluded.