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Can Immunocidin prevent metastasis?
- Mari Maeda
- Sep 7, 2024
- 9 min read
Updated: Mar 5
Max's mom had already lost one dog to bladder cancer, and she felt that he had suffered too much during his chemotherapy treatment.
So, when Max was diagnosed with transitional cell carcinoma (also called urothelial carcinoma), she began to research options and found Immunocidin, a form of immunotherapy.
Soon after the treatment started, Max's symptoms disappeared. He is thriving three years later.
Today, veterinary doctors are using this little-known therapy to help dogs with different types of cancer.
Cougar, a Great Dane, is another dog who was diagnosed with cancer that is not curable with today's standard of care treatment. When he was 6 years old, Cougar was diagnosed with osteosarcoma, a form of bone cancer, and had to have his front leg amputated. Most dogs with osteosarcoma only survive for 10-12 months, even with surgery and chemotherapy. But Cougar received treatment with Immunocidin and survived for over 3 years.
How effective is Immunocidin in helping canine cancer patients? Is it safe? Is there any data supporting its clinical efficacy?
Background
There are many historical records of people with cancer experiencing remission or even cure after severe infections. These instances are rare, but they have been documented for centuries.
One of the most notable examples comes from Dr. William Coley's observations in the late 19th century. He noticed several cancer patients experienced spontaneous remission after developing severe bacterial infections, such as erysipelas (caused by Streptococcus pyogenes). This led to his development of Coley’s toxins, a mixture of killed bacteria (primarily Streptococcus pyogenes and Serratia marcescens) , which he used to deliberately induce fever responses that resulted in tumor regression in many of his patients. While it fell out of favor with the introduction of radiation therapy and chemotherapy, there have been more recent modern attempts to introduce the formulation since its efficacy may be superior to today's conventional therapies.
Another example of bacterial therapy is the BCG vaccine (Bacillus Calmette-Guérin). It was developed in the 20th century by French scientists Albert Calmette and Camille Guérin as a vaccine against tuberculosis (TB) and uses a weakened strain of Mycobacterium bovis, which is closely related to Mycobacterium tuberculosis. The BCG vaccine was first introduced for human use in 1921, and over the years, it has become one of the most widely administered vaccines worldwide. In 1976, BCG was repurposed and introduced as an immunotherapy for bladder cancer. BCG remains one of the most widely used treatments for early-stage bladder cancer due to its ability to harness the body’s immune response for long-term cancer control.
While BCG has been highly effective in reducing the recurrence and progression of non-invasive bladder cancer, some patients become resistant to the treatment. Uncomfortable side effects can also accompany the therapy. To address these problems, the urologist who pioneered the BCG protocol, Dr. Albert L. Morales, began researching alternative therapies. He eventually teamed up with a Canadian group that developed a different bacterial formulation based on mycobacterial cell wall fraction (MCWF). Several clinical trials involving human bladder cancer patients were started, and treatment showed great promise. A form of this formulation eventually became approved for veterinary use and is now called Immunocidin.
What is Immunocidin?
Immunocidin is a drug derived from a bacterial cell wall extract known as mycobacterial cell wall fractions (MCWF). It is available for veterinary use and stimulates the dog’s immune system to target and destroy cancer cells.
The active ingredient of Immunocidin is the purified fragments of cell walls of a soilborne bacterium called Mycobacterium phlei. This bacterium is non-pathogenic (does not cause disease) and is commonly found in the environment, including in soil and on plant leaves.
The cell walls naturally contain high concentrations of compounds that stimulate the immune system, including muramyl dipeptides, trehalose dimycolate, mycolic acid, and glycolipid lipoarabinomannan.
These compounds activate macrophages and other white blood cells and produce cytokines such as IL-6, IL-8, IL-12, IL-18 and TNF-α that help turn on the immune system to fight disease.
The formulation also contains bacterial nucleic acids (e.g. DNA) that have an anti-cancer effect, according to Miriam Cervantes DVM Ph.D., a research scientist at NovaVive.
The diagram below depicts direct and indirect mechanisms of action, including both innate and adaptive immune responses.
The original MCWF formulation was evaluated with human patients and progressed to a Phase 3 clinical trial, but the effort ran out of funds and was terminated before attaining regulatory approval. However, the formulation of Immunocidin for veterinary use was approved by regulatory organizations (including the USDA) for treating mixed mammary tumors and mammary adenocarcinoma in dogs.
Today, a Canadian company, Novavive Inc., produces Immunocidin at a manufacturing site in Athens, Georgia.
Can Immunocidin also help dogs with other types of cancer?
Immunocidin is a strong immunostimulant that can be used to treat different cancer types.
According to Graeme McRae, the president of NovaVive and one of the inventors of Immunocidin, the therapy was initially evaluated to treat mammary tumors, even though there were indications that it could be effective for bladder cancer and other types of cancer. To obtain regulatory approval for anticancer therapy, the product must be tested for safety and show some efficacy in a specific tumor type(s). Hence, mammary cancer was initially selected for evaluation.
New studies are examining how immunocidin might help canine patients with osteosarcoma, bladder cancer, and other tumor types (see below).
It's important to note that because immunocidin is a fully approved therapy, it can be ordered by vets in North America and used "off-label" to help dogs with other types of cancer. It is not necessary to be part of a clinical study to be treated with Immunocidin.
How is it administered?
Immunocidin was initially evaluated and approved as an intra-tumoral injection treatment.
Veterinarians also use new protocols, administering it through IV infusion and oral doses.
What kind of side effects could a dog experience?
Some dogs might experience lethargy, fever, or vomiting, depending on how the product is administered and their level of sensitivity. If Immunocidin is injected into the tumor, there may be some injection site pain, and discharge from the tumor as it breaks down.
What are the different ways immunocidin might help dogs with cancer?
There are several different ways that Immunocidin may be used.
It may help dogs who cannot get surgery or other standard-of-care treatment. (For example, a dog who cannot go under anesthesia and get surgery to remove malignant mammary tumors)
It may be used in conjunction with conventional treatment to slow cancer growth and lower the risk of metastasis. (For example for dogs with osteosarcoma that might undergo amputation and chemotherapy treatment, Immunocidin may slow or lower the risk of metastasis).
It may be used to help dogs experiencing recurrence or who did not respond to prior therapy.
What does Immunocidin's anti-cancer efficacy depend on?
How well it works depends on many factors, including:
-the dog’s overall health and health of the immune system.
-aggressiveness of tumor and tumor microenvironment
-the dosage, how it’s administered, and the frequency of administration.
-whether it is administered before the surgery as a neoadjuvant or after surgery
-whether it is combined with chemotherapy or other therapies
Researchers are still trying to find ways to improve Immunocidin efficacy.
Other advantages?
Immunocidin can be ordered and administered at a regular veterinary clinic. This is an important factor, considering not all canine patients are cared for by veterinary oncologists because of long appointment wait times, living too far from a specialty hospital, or due to financial reasons.
Another advantage is that the treatment is relatively inexpensive, especially compared to chemotherapy.
Osteosarcoma and Immunocidin Treatment
Canine osteosarcoma (OSA) is a highly aggressive form of bone cancer that typically occurs in limbs but can also affect other bones in the body, such as the jaw or pelvis. OSA treatment includes a combination of surgery, chemotherapy, and/or radiation therapy. However, even with these treatments, OSA is known for spreading, especially to the lungs. For example, median survival time with limb amputation and chemotherapy is extended to about 10 to 12 months.
Immunotherapy treatments can help extend survival times for dogs with osteosarcoma. Recently published examples include the use of a genetically modified Listeria bacteria-based vaccine from the University of Pennsylvania and the EGFR/HER2 vaccine.
Immunocidin may also help dogs with OSA, according to a study published by Dr. J Mangieri.
OSA is known for its rapid progression and high potential for metastasissteosarcoma is an aggressive In several case studies, Immunocidin has been shown to help extend survival times for dogs with osteosarcoma. In some of these cases, Immunocidin was used alone. In others, Immunocidin was combined with chemotherapy.
There is an ongoing proof-of-concept study in canine osteosarcoma with Immunocidin. If the results are positive, a more comprehensive study in this tumor type will be launched in the near future.
See a summary of a previous study led by J. Mangieri et al, "Efficacy of Mycobacterial Cell Wall Extract (MCWE) in the treatment of osteosarcoma in dogs" (MCWF used to be called MCWE).
and a study led by Jeannette Kelly DVM, "Concurrent use of chemotherapy with Immunocidin for treatment of canine lymphoma and osteosarcoma"
A new study is accepting patients diagnosed with osteosarcoma.
Bladder Cancer or Transitional Cell Carcinoma (TCC)
Transitional cell carcinoma (TCC) or Urothelial carcinoma is the most common form of urinary bladder cancer in dogs, and represents 2% of all reported canine cancers.
In a study published in 2017 (Filion et. at), five canine patients were treated intravesically (product was infused into the bladder through a catheter). The publication describes the treatment regimen and the patients' responses.
Susie was diagnosed with bladder cancer or Transitional Cell Carcinoma (TCC), also known as urothelial carcinoma, in 2021. Because of her age, her parents decided not to get chemotherapy or piroxicam treatment.
Her doctor then recommended immunotherapy with Immunocidin.
In the beginning, they traveled every three weeks to have Immunocidin introduced directly into Susie's bladder.
They also completely changed her diet and began cooking for her every day and added supplements like Turkey Tail too.
The initial diagnosis was three to six months, but Susie was doing well, almost two years after her diagnosis!
Novavive is working on a protocol for a study in dogs diagnosed with TCC.
* “The in-vitro and in-vivo anti-cancer potential of mycobacterium cell wall fraction (MCWF) against canine transitional cell carcinoma of the urinary bladder” Filion CM, Rodrigues L, Johannes C, Masic A, 2017
Hemangiosarcoma
In a paper published in xxx, researchers treated n dogs with splenic hamangiosarcoma with Immunocidin.
Due to side effects observed in patients, they terminated the trial early and concluded that efficacy could not be observed.
We recently spoke a veterinarian in Canada and the dog parent - whose hemangiosarcoma went into long term remission with the help of Immunocidin treatment.
Other cancer types and other animals
Immunocidin has been used to treat individual dogs with anal sac adenocarcinoma, hemangiosarcoma, lymphoma, soft tissue sarcoma, histiocytic sarcoma, as well as other cancer types using IV infusion [Jeanette Kelley 2018]
There is an ongoing study enrolling patients with solid tumors to see if Immunocidin (combination of IV and oral dosing) might also improve quality-of-life as part of a palliative treatment.
Where can my dog get Immunocidin treatment?
A veterinary clinic in the US, Canada, and UK can order Immunocidin. For other locations, please contact Novavive.
Immunocidin can be used to treat mammary tumors, and it can be used off-label to
Pet parents and veterinarians can contact NovaVive directly to see if their dog might be eligible to enroll in one of the ongoing studies. If the pup is part of a study, the cost of the Immunocidin (but not the veterinary clinic treatment costs) may be covered by NovaVive.
How is Immunocidin compare with other immunotherapy treatments for dogs with cancer?
Both help dogs by activating the immune system, but there are big differences.
The Yale vaccine activates the immune system to target specific proteins called EGFR/HER2 that are commonly expressed on the tumor cell surfaces. So, its efficacy may be limited to tumor types associated with the over-expression of EGFR/HER2 proteins.
Also, because it triggers an adaptive immune response, the antibodies can take 2-3 weeks to build up.
Immunocidin activates both the innate and adaptive immune response, so a wait is not needed for the immune response. It also contains bacterial DNA that can directly kill cancer cells without relying solely on the immune system. Unlike the Yale vaccine treatment which consists of only two injections, Immunocidin treatment is often customized and may require initial and maintenance treatments consisting of weekly or monthly administration, depending on the patient.
Based on my conversations with Professor Mamula at Yale University and Graeme McRae of NovaVive, it may be that the two immunotherapy treatments are synergistic.
A great deal remains to be learned from further studies to see how each or in combination can best help dogs.
"My vet has never heard of Immunocidin"
I find it quite surprising that relatively few veterinarians know about Immunocidin, even though it’s been available for over 20 years.
One reason for the obscurity is that the previous owner of NovaVive, Bioniche Life Sciences, focused human health instead of veterinary therapies for pets. NovaVive has owned the technology since 2014 and has put a renewed emphasis on veterinary treatment.
NovaVive can provide detailed information about Immunocidin and various peer-reviewed published study results.
How can I learn more about studies involving Immunocidin?
Contact NovaVive and speak with Graeme McRae or Dr. Miriam Cervantes for additional information.
Phone: (613) 308-9788
Email: info@NovaVive.ca
If you have any questions, please email info@ccralliance.org .
All information here is for educational purposes only. It's not intended to be a substitute for professional veterinary advice. Always seek guidance from your veterinarian regarding your pet’s health or medical condition.
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