Canine Cancer vaccine developed by a Yale University team is helping dogs fight cancer where other treatments have failed.
I first learned about new vaccine-based immunotherapy created by Yale University researchers from a mom of a brave six-year-old St Bernard fighting cancer.
Stitch had his leg amputated after osteosarcoma diagnosis last winter, roughly a year ago. Despite all efforts, including keto-diet and immune-boosting herbal medicine, he was showing signs of lung metastasis by the summer. His mom, Amee Gilbert, was looking for options to help extend his life and came across Dr. Mark Mamula’s trial.
After learning about the vaccine, I reached out to Dr. Mamula to learn more about his project. I also researched the background publications and spoke with several pet parents who were trying the vaccine.
I was intrigued by the number of dog owners who were trying the cancer vaccine, and by how very few people in the veterinary oncology community knew about the trial.
Here is a summary of the Yale Canine Cancer Vaccine.
Why is Yale EGFR/HER2 Vaccine important?
Today’s standard-of-care treatment mostly relies on surgery, chemotherapy, and radiation therapy.
Unless cancer is found extremely early, these treatments usually only provide temporary relief to cancer’s progression.
Immunotherapy (including cancer vaccines) has the potential to produce very long remission times and possibly reversal of metastasis.
Who developed the Yale Canine Cancer Vaccine?
A research team developed the vaccine at Yale University: Dr. Mark Mamula, a professor with the School of Medicine and Dr. Hester Doyle, a research scientist. They are experts in immunology, and their vaccine is the result of decades of work in understanding how the immune system is turned on or off.
What are the possible benefits of this vaccine treatment?
Many dogs have experienced control of cancer growth and reversal of growth.
Some dogs with osteosarcoma have also experienced a reversal of pulmonary metastasis.
According to Dr. Mamula:
"We have had some patients with a very good outcome, though obviously, we can’t guarantee that for every patient. Much of the outcome depends on factors such as age, tumor type, the extent of the disease, and many other factors that we don’t fully understand yet”
Can vaccines be used to heal a body? I thought vaccines are for prevention.
Vaccines mobilize the body’s immune system to recognize and go after tumor cells as well as bacteria and viruses. Vaccines can be preventive or therapeutic. So they can also be used to control and fight cancer.
How does Yale Canine Cancer Vaccine help fight cancer?
EGFR and HER2 proteins are often over-expressed by tumor cells.
On the surface of tumor cells, roughly 10x to 100x more of these proteins are found compared to normal healthy cells. This over-expression is associated with aggressive tumor growth and poor prognosis.
With the injection of Yale vaccine, the dog’s immune cells become trained to recognize cells displaying EGFR proteins as ‘bad’ cells and to attack them.
The vaccine is made up of a short chain of amino acids (called peptides) which is part of the larger EGFR and HER2 protein. The same vaccine can target cells over-expressing EGFR and/or HER2 proteins on the surface.
The vaccine boosts the generation of antibodies that bind to EGFR/HER2 and inhibits intracellular signaling and inhibits tumor growth. The vaccine may also boost the population of cancer fighting T-cells.
Which veterinary clinics provide this treatment?
Originally, Yale team partnered with a veterinary oncology clinic in Connecticut to evaluate the safety and efficacy of the vaccine. After launching the trial in 2016 and seeing positive results, the team made it possible for pet owners in different states to participate in the trial. The vaccine was shipped to the local veterinary clinics.
At the moment (Dec 2020), the clinical trial has been paused.
Once the team receives a provisional licensing from the USDA (the regulatory agency that oversees immunotherapy drugs in the USA), the study will resume.
(If you would like to be notified when the study resumes, please send an email to email@example.com and we will let you know as soon as the study is enrolling patients again).
How is the treatment given to the patients?
1. The vaccine is shipped to a local veterinarian in loaded syringes.
2. The vet administers two subcutaneous injections three weeks apart. Blood samples are also collected on these days and shipped to Yale University lab for analysis.
3. The third blood sample is collected on day 45-50 and sent to Yale University lab for analysis.
Which types of cancer are the vaccine being used for?
Currently, the vaccine is being offered to patients with
And other tumor types known to over-express EGFR/HER2
What are the requirements to be part of the trial and receive the treatment?
Compared to other trials involving veterinary patients, the requirements for this trial is minimal.
-The dog with one of the cancer types above needs a confirmed diagnosis.
-It accepts patients who have not had any prior treatments.
-It accepts patients who have had prior treatments, such as surgery and chemotherapy.
-If the dog is on chemotherapy, a waiting period of 3 weeks is needed after the last chemo cycle before the administration of the vaccine. (This is because chemo can suppress the immune system)
-A signed consent form is required.
Can a dog with metastasis receive this vaccine?
Yes. Researchers are particularly interested in patients with evidence of metastatic disease in the lungs or elsewhere.
Are there any side effects?
According to Dr. Mamula, the observed side effects have been minimal.
20-25% of dogs develop sterile abscess, a large lump near the injection site. This is not an infection but is due to inflammation - a sign that immune system is doing its job. It may ooze but will eventually resolve on its own, without causing any discomfort to the dog. Use of warm compresses help.
How much does the treatment cost?
There is no charge for patients who can come to their partnering clinic in Connecticut. For other patients, they are requesting a tax-deductible donation of ~$1000 to their program through Yale University, to cover the cost of vaccine and lab analysis. Pet parents are also responsible for the payment for exams and vaccine injection at the local veterinary clinic. Sometimes, donation ‘requirement’ waived for those who cannot afford it.
Is there any published data about the vaccine’s safety and efficacy?
There is published data with mouse model, but no peer-reviewed journal publication for the canine study.
Dr. Mamula’s team is now working on a publication based on the data that has been collected so far. To better quantify their findings, the team is also making an effort to follow up with pet parents and obtain x-rays records so that disease progression can be monitored over time.
(CCRA is providing financial support to the Yale research project to facilitate additional data collection)
Also, Professor Mamula gave a lecture on Oct 3, 2020 summarizing his work. The slides and recording are available here.
Are some dogs experiencing durable remission?
Yes. Some canine patients who had run out of options are experiencing long-term remissions.
Codi was nine years old when he was diagnosed with osteosarcoma. In August 2017, he had surgery to have his leg amputated at a clinic in Red Bank, New Jersey.
But eight months after his surgery, his cancer had metastasized into a golf-ball-sized tumor in his lung. His dad found about the vaccine trial doing a google search and took him to Connecticut.
The use of the vaccine resolved the metastasis, and the sign of cancer disappeared.
Today, Codi became a thriving tripawd, and survived for over two years after his metastasis was discovered.
Sadly, Codi was diagnosed with a different cancer - hemangiosarcoma- in his liver in August 2020, and passed away.
But he had excellent quality of life after the vaccine induced resolution of his pulmonary metastasis and all signs of osteosarcoma disappeared.
Jethro, a three-year-old pup, was diagnosed with hemangiosarcoma in Mar 2019. He received the vaccine treatment and is thriving with no sign of cancer.
There are many dogs who responded positively to the vaccine, but there are also many dogs whose survival times did not get extended with the vaccine.
Because the Yale team is still conducting a pilot trial and has not released any data, we do not know what fraction of dogs receiving the therapy is experiencing long-term remission.
We are looking forward to the publication of their findings and future work so we can learn answers to questions such as:
For which tumor types is the vaccine most effective? And what percentage of patients are experiencing durable remission?
Is the vaccine more effective combined with chemotherapy and other treatments, or can it be effective on its own?
Can the blood test (and measuring the antibodies) reliably predict which patients are going to respond to the treatment?
Have any patients experienced any severe side-effects?
What research is needed to increase the number of responding patients?
What research is needed to extend the survival times?
Once the publication and data become available, I will be providing an update.
Can a dog with metastasis receive this vaccine?
Researchers are particularly interested in patients with evidence of metastatic disease in the lungs or elsewhere.
There are several dogs whose pulmonary metastasis was reversed, including Codi described above.
Ranger is another lucky dog.
Ranger’s dad shared this post on Facebook recently (shared here with his permission):
“Many of you have read my posts about the journey Ranger and I have been on since his being diagnosed last spring with osteosarcoma.
Like many of you, I went through the shock and devastation of the disease and the odds, the sudden in-depth reading about the disease, the agony of deciding to amputate, the tough two weeks after the amputation questioning if it was the right thing to do, the copious home remedies to try, and the seeking of any current medical miracles.
For those of you who are new, he was diagnosed last March (2019), went through 4 rounds of carboplatin after his amputation.
It was after the carboplatin that a lung met showed.
I got him into the clinical trial at Ohio State, an experimental drug called Procaspase-1, along with more chemo (4 rounds of doxorubicin).
At the end of the trial, the metastasis had grown from 9 mm to 12 mm.
Before the end of that clinical trial, I had read about the Yale Canine Cancer Vaccine Clinical Trial. I decided to see if he would be eligible for it.
Dr. Mamula graciously said that he was, and in November, he got his two vaccine shots. Ranger had a very positive response.
On December 24th, he went back to OSU for follow-up x-rays. The lung met appeared to have become static.
Ranger and I went back to OSU this morning for another follow-up. The news....they cannot see the tumor anymore on the x-ray. …
I am so very thankful for this research, and all the Yale Team does. I thank all of you for your support as we are a family. I know that the journey is not over...but we will continue to battle. ... And I will continue prayers for all of you and your pups. Thank you again Mark!!!!!!! Ranger sends his love.”
It is not known what percentage of dogs with lung metastasis has responded as well as Ranger has.
Quantitative, data-based information is needed for the vaccine to be approved for future commercialization and to be broadly accepted and used at veterinary clinics.
How do I arrange for this vaccine treatment for my dog?
You can contact Dr. Mamula directly.
There is also an active Facebook group for Yale Canine Cancer Vaccine https://www.facebook.com/groups/620190395093636/?ref=bookmarks .
Although it was too late for the brave St Bernard, Stitch, to receive the vaccine, Stitch’s sister Lilly who was also diagnosed with osteosarcoma recently received the vaccine treatment. We are rooting for you Lilly!
This blog is dedicated to Stitch, a very special dog.
Thank you for reading! Please leave comments and questions.
What roles do EGFR and HER2 proteins play in cells?
EGFR stands for Epidermal Growth Factor Receptor. They are found on the surface of cells and are involved in triggering cell division and proliferation. EGFR is also known as HER1.
HER2 stands for Human Epidermal Growth Factor 2 and also helps control how cells divide and grow.
Overexpression of these receptor proteins on the cancer cell surface is caused by the mutation in EGFR or HER2 genes, and can result in the cells that divide uncontrollably, can invade other tissues, and can trigger angiogenesis (formation of new blood vessels needed for tumor metastasis)
How does the Yale vaccine help the immune system target cancer cells?
When the Yale vaccine is injected, the dog’s immune system produces antibodies and T-cell response, attacking tumor cells displaying EGFR/HER2 proteins.
The vaccine is made up of a short chain of amino acids (called peptides) that is part of the larger EGFR protein.
Because there is enough similarity between the family of proteins targeted by the vaccine, the same vaccine can be used to activate the immune system to kill cancer cells that are over-expressing EGFR, HER2, HER3 and HER4 proteins on the surface.
Dr. Mamula and Dr. Doyle studied the cancer-fighting impact of the vaccine with mouse models before they began their trial with canine patients.
Are researchers collecting and analyzing tumor samples?
Yes. They have recently begun to collect and analyze tumor samples patients so they can analyze the molecular expression patterns for different dogs.
This may help them understand why some dogs might experience a much longer remission compared to others and make future improvements. It might be found that the vaccine works best only for dogs with over-abundance of EGFR and related proteins.
If canine tumors express EGFR, could EGFR inhibitor be used against cancer?
EGFR inhibitors are monoclonal antibody developed for human patients and are very expensive.
Publications on canine use of EGFR inhibitors are inconclusive.
What other immunotherapy treatments are there for canine patients?
For osteosarcoma patients, a new ‘personalized’ immunotherapy is available from ELIAS Animal Health. You can read more about this treatment here.
In their pilot trial, roughly half of the dogs who completed their treatment experienced extremely long remission times.
Their treatment includes the use of a vaccine made from the dog’s own tumor cells and infusion of activated cancer-fighting T-cells.
Roughly thirty veterinary oncology clinics in the US offer this treatment today.
Also, for osteosarcoma patients, a listeria-based vaccine targeting HER-2 overexpression was tested in a pilot trial , led by the University of Pennsylvania team.
The results were quite impressive and led to the launch of two new expanded clinical trials. One trial launched by Aratana Therapeutics (last year acquired by Elanco) was recently closed. This was very bad news to all pet parents and to the veterinary oncology community, which had been hoping for good results.
CCRA is working with different research groups to launch additional trials to help pet patients.