%20(2).png)
In the 1890's, a New York city physician Dr. William Coley realized cancer cures might be possible - even for late-stage patients - after experiencing a bacterial infection.
He wasn’t the first person to notice this; other physicians in Germany had recorded similar occurrences.
But Dr. Coley was the first to create a new therapy using a mixture of weakened bacteria and began treating hundreds of patients.
The result was remarkably successful.
He also shared the formulation of the so-called “Coley’s toxin” with other doctors, many of whom were also able to help patients.
It wasn’t known at the time, but Coley had created a form of cancer immunotherapy – a way of fighting cancer by stimulating the patient’s immune system to kill tumor cells.
But unfortunately, due to the introduction of radiation therapy and chemotherapy, Coley’s toxin fell by the wayside. Today, Coley’s toxin is no longer available in the US or Canada.
(Although there have been attempts to revive its production, getting regulatory approval has been impossibly hard).
The nearest thing to Coley’s toxin that is currently clinically used is called BCG (Bacillus Calmette-Guerin), to treat bladder cancer patients. For roughly 70% of patients with early-stage bladder cancer, BCG treatment can effectively stop cancer recurrence.
But because BCG consists of living bovine tuberculosis bacteria, there is a finite possibility of harming the patient with an unwanted infection and also causing serious complications. BCT also tends to be poorly tolerated by some patients.
Is there a safer alternative?
Since the 1960s, researchers have been studying cell walls of bacteria that contain many different compounds that stimulate our immune system.
One of these technologies, called Mycobacterium Cell Wall Fraction (MCWF), has been developed into anticancer immunotherapy - Immunocidin - for veterinary use.
The same technology was developed into a human bladder cancer formulation that progressed to Phase III clinical testing.
In the 1990s, Immunocidin was approved by regulators in the US and Canada for treating mixed mammary tumors and mammary adenocarcinoma in dogs.
A small Canadian company, NovaVive Inc., produces Immunocidin today (at a manufacturing site in Athens, GA).
Can Immunocidin also help dogs with other types of cancer?
MCWF is a strong immunostimulant, with the potential to treat different cancer types, regardless of the location or origin.
(Coley’s toxin was also used to treat many types of cancer)
According to Graeme McRae, the president of NovaVive and one of the inventors of Immunocidin, the product was first tested to treat mammary tumors, even though there were indications that the formulation could be effective for other cancer types. In order to obtain regulatory approval for anticancer therapy, the product must be tested for safety and show some efficacy in a certain tumor type.
New studies are evaluating how Immunocidin might help canine patients with osteosarcoma, bladder cancer, and other tumor types (see below).
It's important to note that veterinarians are permitted to use regulator-approved therapies to treat other types of cancer (“off-label”) if they are comfortable doing so and believe it may help their patients.
What’s in Immunocidin and how does it work?
The active ingredient of Immunocidin is the purified fragments of cell walls from 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 the leaves of plants.
The cell walls naturally contain a high concentration 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.
How is it administered?
Immunocidin was initially approved for intra-tumoral injection treatment.
Newer protocols, currently under study, involve administering the product by IV infusion and as an oral dose.
What kind of side-effects might there be?
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 there may be discharge from the tumor as it breaks down.
In what ways might Immunocidin help dogs with cancer?
Immunocidin may:
-help a dog who is not a candidate for receiving surgery or other standard-of-care treatment
-help a dog who has relapsed or did not respond to a prior therapy,
-help recurrence of cancer.
What does its anti-cancer efficacy depend on?
How well it works depends on many factors, including:
-the dog’s overall health especially his or her immune system
-the 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 trying to answer these and other questions.
Other advantages?
Because Immunocidin is not a toxic agent like chemotherapy, it can be administered at a regular veterinary clinic (and not just at a specialty referral center that for some patients might be hours away). If the oral administration route is selected, the dog can receive the therapy at home.
Another advantage is that it is relatively inexpensive especially compared to chemotherapy.
Are there studies enrolling patients?
*Osteosarcoma
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.
*Transitional Cell Carcinoma or TCC (Bladder cancer)
Transitional cell carcinoma (TCC) 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 etal *) , five canine patients were treated intravesically (product was infused into the bladder through a catheter). The publication describes the treatment regimen and the response in the patients.
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
*Other cancer types
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?
If a veterinarian thinks Immunocidin might help a patient, it can be ordered in the US, Canada, and UK.
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 different from Yale's EGFR/HER2 vaccine?
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, it can take 2-3 weeks for the needed antibodies 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 (research scientist) for additional information for you and your vet.
Phone: (613) 308-9788
Email: info@NovaVive.ca
If you have any questions, please email info@ccralliance.org .
All information here is for informational and educational purposes only. It's not intended to be a substitute for professional veterinary advice. Always seek guidance from your veterinarian with any questions you may have regarding your pet’s health or medical condition.