Harnessing nature's precision weapon to fight cancer in our four-legged companions
In the world of cancer research, some of the most promising advances come from unexpected places. Imagine if a virus that affects rabbits could help save dogs from cancer—and potentially pave the way for human treatments too. This isn't science fiction; it's the cutting edge of oncolytic virotherapy, where viruses are harnessed to selectively target and destroy cancer cells while leaving healthy tissue unharmed. For the millions of dogs diagnosed with cancer each year—and the families who love them—this approach represents new hope where traditional treatments often fall short. Particularly for canine soft tissue sarcomas, which pose significant treatment challenges, an innovative approach using modified myxoma virus offers a fascinating glimpse into the future of veterinary medicine and beyond 1 .
Myxoma virus (MYXV) belongs to the poxvirus family and has several inherent characteristics that make it an excellent candidate for oncolytic virotherapy. First and foremost, it's exceptionally safe from a species perspective: MYXV only causes disease in rabbits, meaning it's completely harmless to humans, dogs, and other vertebrates 1 . This species specificity provides a built-in safety mechanism for its use in non-lagomorph species.
Unlike many other viruses, poxviruses don't require specific cellular receptors to infect cells, which means they can potentially target a wide variety of cancer types 1 . Additionally, they naturally tend to accumulate in areas of tumor neovascularization—the new blood vessels that tumors create to sustain their growth—making them excellent at homing in on cancerous tissue 1 .
Another advantage of MYXV is its large, linear, double-stranded DNA genome, which allows for extensive genetic modification without compromising the virus's ability to replicate 1 . For the studies discussed here, researchers used a modified version of myxoma virus called MYXVΔserp2, which has the serp2 gene deleted. This particular gene deletion serves two important purposes: it makes the virus even safer (highly attenuated in rabbits) while simultaneously enhancing its cancer-fighting abilities in non-lagomorph species 1 3 .
An important safety feature of poxviruses is that their DNA remains in the cytoplasm of host cells and doesn't integrate into the host's genetic material, eliminating the risk of insertional mutagenesis that could potentially lead to new mutations 1 . Furthermore, poxviruses stimulate strong immune responses that lead to rapid viral clearance from the body, preventing latent infections that could cause problems later 1 .
While mouse models have long been the standard for cancer research, they have a significant limitation: they're poor predictors of how humans will respond to treatments, especially when it comes to oncolytic viruses 1 2 . This is where dogs with spontaneously occurring cancers offer a unique advantage.
Canine cancers develop naturally in a complex immune system environment, much like human cancers do. The genetic diversity of dogs (different breeds, sizes, and genetic backgrounds) better reflects human population diversity than inbred laboratory mice. Additionally, dogs share our environment and often receive comparable healthcare standards when participating in clinical trials, making them exceptional models for studying cancer treatments 1 .
Soft tissue sarcomas (STS) are a group of cancers that arise from connective tissues such as fat, muscle, nerves, and fibrous tissues. In dogs, these tumors are often locally aggressive, meaning they tend to invade surrounding tissue, making complete surgical removal challenging. Even when surgeons believe they've removed all visible tumor tissue, microscopic cancer cells often remain, leading to tumor regrowth in approximately one year 3 .
The location of these tumors often makes them not amenable to complete surgical resection, especially when they're large or located in anatomically constrained areas 1 . While radiation and chemotherapy are sometimes used after surgery, these treatments often only slow down rather than prevent recurrence, highlighting the critical need for more effective treatment options 3 .
Dogs develop cancer at roughly the same rate as humans, with over 6 million new cancer diagnoses in dogs each year in the United States alone. This makes them invaluable partners in the fight against cancer.
In 2018, researchers from Colorado State University published a pioneering study evaluating the safety of MYXVΔserp2 in dogs with spontaneously occurring soft tissue sarcomas 1 2 . This study was critical because while previous research had shown that oncolytic viruses could infect and kill canine cancer cells in laboratory dishes and mouse models, there was limited data on their safety in actual canine patients 1 .
The study had two primary objectives: first, to evaluate the safety profile of MYXVΔserp2 treatment in dogs with STS, and second, to determine its immunogenicity (how well it stimulates an immune response) 1 2 . To address these questions, the researchers designed a trial with ten canine patients divided into two treatment groups:
| Group | Number of Dogs | Tumor Status | Treatment Approach | Virus Dose |
|---|---|---|---|---|
| Intratumoral | 5 | Unresected tumors | Single direct injection into tumor | 10⁶ PFU in 1 mL PBS |
| Post-operative | 5 | Marginally excised tumors | Injection around surgical site at 2 cm intervals | 5-10 doses of 10⁶ PFU each |
The dogs enrolled in the study had to meet specific criteria to ensure their safety and the study's validity. All dogs had histologically confirmed soft tissue sarcomas, and their owners agreed not to pursue any additional cancer treatments (chemotherapy, radiation, etc.) until the study was completed or their cancer progressed 1 .
Researchers implemented meticulous monitoring protocols. For the intratumoral group, veterinarians conducted extensive examinations—daily for the first week and then weekly until Day 28-30 post-treatment 1 . They collected a wide array of samples to assess potential virus spread and immune response:
The research team used quantitative PCR to detect viral DNA in the various samples collected, which allowed them to determine whether the virus was spreading beyond the injection site 1 . They also measured anti-MYXV antibodies in blood samples to assess whether the dogs' immune systems were mounting a response against the virus 1 .
The most encouraging finding from the study was that no detrimental effects of MYXVΔserp2 treatment were observed in any of the ten canine patients 1 2 . The dogs tolerated the treatments well, with no signs of illness attributable to the virus administration.
Comprehensive blood work revealed no clinically significant changes in complete blood profiles, serum chemistry analyses, or urinalyses 1 . This was particularly important because it suggested that the virus wasn't causing damage to major organs like the liver or kidneys, addressing concerns about potential systemic toxicity.
A crucial safety aspect of any viral therapy is ensuring that the virus doesn't spread to unintended locations in the body or into the environment. In this study, researchers found that viral DNA was isolated from only one tumor swab out of all the samples collected 1 . Importantly, no viral DNA was detected in blood, urine, or feces at any time point, indicating that the virus wasn't spreading systemically or being shed into the environment 1 .
The immune response to the virus was variable among the dogs. Anti-MYXV antibodies were occasionally detected, but not consistently in all animals 1 . This suggested that while some dogs mounted an immune response to the virus, it wasn't universal, and the response didn't appear to cause adverse effects.
| Parameter Measured | Results | Interpretation |
|---|---|---|
| Clinical symptoms | No virus-related adverse effects | Treatment well-tolerated |
| Blood work | No clinically significant changes | No organ damage or toxicity |
| Viral DNA in blood/urine/feces | Not detected | No systemic dissemination |
| Viral DNA in tumor swabs | Detected in 1 sample | Limited local persistence |
| Anti-MYXV antibodies | Occasionally detected | Variable immune response |
The promising safety profile of MYXVΔserp2 opened the door for further research exploring combination therapies. In a more recent study published in 2023, researchers investigated whether combining MYXVΔserp2 with oclacitinib (a JAK1 inhibitor medication) could enhance the virus's effectiveness 3 .
The rationale behind this combination was fascinating: prior research had shown that type I interferons (powerful antiviral signaling proteins) can limit myxoma virus replication in cells 3 . Since cancer cells sometimes retain their antiviral defenses, suppressing these defenses might allow the virus to replicate more extensively within tumors, leading to better cancer destruction.
Oclacitinib, marketed under the name Apoquel®, is typically used to treat allergic diseases in dogs by inhibiting certain immune signaling pathways 3 . Importantly, it doesn't significantly suppress the T helper 1 immune responses that are important for antiviral immunity and cancer surveillance 3 .
In the combination study, dogs with high-grade soft tissue sarcomas received oclacitinib for 14 days starting approximately one week before surgery 3 . After tumor removal, they received MYXVΔserp2 at the surgical site at two time points to target any remaining cancer cells.
The results showed that tumor regrowth in dogs treated with the virus was decreased compared to historical controls, which was encouraging 3 . However, the addition of oclacitinib didn't further inhibit regrowth beyond what was achieved with virus alone 3 . This suggests that while MYXVΔserp2 itself has anticancer activity, the specific approach of JAK inhibition didn't provide additional benefit in this context.
| Aspect | Traditional Mouse Models | Canine Spontaneous Cancer Models | Implication for Research |
|---|---|---|---|
| Tumor development | Artificially induced | Natural development in immune-competent hosts | More realistic tumor microenvironment |
| Genetic diversity | Limited (inbred strains) | High (different breeds) | Better reflects human population diversity |
| Predictive value for humans | Poor for oncolytic viruses | Potentially better | More reliable translation to human trials |
| Dual benefit | Primarily preclinical research | Benefits both dogs and human medicine | Ethical advantage with dual species benefit |
To conduct these sophisticated studies, researchers rely on specialized reagents and tools. Here are some of the key components used in oncolytic virotherapy research:
The research exploring myxoma virus as a cancer treatment for dogs with soft tissue sarcomas represents a fascinating convergence of virology, oncology, and comparative medicine. The studies conducted so far provide compelling evidence that MYXVΔserp2 is safe for use in canine patients, with no detectable systemic spread or significant adverse effects 1 2 .
While much research remains to be done—including larger trials to establish efficacy and optimize treatment protocols—these early findings offer hope for both veterinary and human medicine. The approach highlights the value of studying spontaneous cancers in companion animals as a bridge between laboratory models and human patients.
As research continues, we move closer to a future where viruses specifically designed to target cancer cells become standard weapons in our therapeutic arsenal—offering new options for patients facing cancers that are currently difficult to treat. For our canine companions and their families, that future can't come soon enough.