Yale's EGFR/HER2 Vaccine Helps Dogs With Metastasis?!

(Please go to this page for the current study status)

A canine cancer vaccine developed by a Yale University team is helping dogs become long-term survivors where other treatments have failed.

I first learned about this new vaccine-based immunotherapy created by Yale University researchers in 2019 from a friend whose six-year-old St Bernard was fighting cancer.

Stitch had his leg amputated after his osteosarcoma diagnosis. Despite all efforts, he was already showing signs of lung metastasis.

His mom, Amee Gilbert, began looking for options to help him and came across Prof. Mark Mamula’s trial.

Stitch was diagnosed with osteosarcoma in winter of 2018 but by the summer of 2019, cancer had spread to his lungs.

Here is a summary of the Yale Canine Cancer Vaccine.

What are the benefits of Yale EGFR/HER2 Vaccine?

Today’s standard-of-care treatment largely relies on surgery, chemo, and radiation therapy.

For many canine patients, conventional treatments usually only provide temporary relief to cancer’s progression.

For example, dogs who are diagnosed with osteosarcoma only have a median survival time of around 12 months, even after surgery and chemotherapy.

Cancer therapeutic vaccines and other immunotherapy treatments have the potential to produce very long remission times, stopping and reversing metastasis for some of the dogs.

With this Yale EGFR/HER2 vaccine, many dogs have experienced delays in cancer growth.

In a few remarkable cases, dogs with osteosarcoma have also experienced a reversal of pulmonary metastasis.

According to Dr. Mamula, the researcher responsible for the development of the therapy:

"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”

Who developed the Yale Canine Cancer Vaccine?

A research team led by Professor Mark Mamula at the Yale University School of Medicine created the vaccine.

Professor Mamula and research scientist Dr. Hestor Doyle are immunologists. For decades, they have been studying how the immune system figures out which cells to tolerate and which cells to attack. Their work originally focused on auto-immune diseases such as lupus and diabetes but their attention turned to cancer as they explored how to 'break immune tolerance'- which is critical for cancer treatment.

Dr. Hester Doyle and Professor Mark Mamula of Yale University School of Medicine

Aren't vaccines used for prevention, not treatment?

We are most familiar with preventive vaccines such as those for COVID-19 or the flu.

But vaccines can be designed for treating cancer since they can mobilize the body’s immune system and help the immune system form long-term memory of targets to attack.

How does EGFR/HER2 Vaccine work?

EGFR (Epidermal Growth Factor Receptor) and HER2 (Human Epidermal Growth Factor 2) are proteins often found in over-abundance on the surface of cancer cells caused by undesired mutation.

This means that on the surface of tumor cells, roughly 10x to 100x more of these proteins are found compared to normal healthy cells.

This over-abundance causes cells to divide uncontrollably and helps the formation of new blood vessels needed for cancer to spread and invade other tissues.

EGFR/HER2 over-expression is associated with very aggressive tumor growth and poor prognosis for most cancer types.

Tumor cell (right) with over-expression of HER2 receptors which is associated with aggressive tumor growth, and poor prognosis.

With the injection of the Yale vaccine, the dog’s immune cells become trained to recognize cells displaying EGFR or HER2 proteins as ‘bad’ cells and to attack them.

Specifically, the vaccine boosts the generation of antibodies that bind to EGFR/HER2 and inhibits intracellular signaling and inhibits tumor growth. The vaccine also boosts the population of cancer-fighting T-cells.

The vaccine itself is made up of a short chain of amino acids or peptides that are part of the larger EGFR and HER2 protein.

The vaccine was designed so that it could help the immune system recognize EGFR(HER1), HER2, as well as HER3 and HER4 proteins, widening the target coverage.

What is the status of this study?

After launching the trial in 2016 and seeing promising results, the team made the vaccine available widely. To date, about 600 dogs with different cancer types and stages have been treated with the vaccine. And information about safety and efficacy has been shared in several peer-reviewed publications and conference presentations.

The new study is opening at clinics, starting in Washington State. Wide-scale availability is expected later in 2023. You can sign up to be notified by email updates. We will also be updating the linked page with the updated status.

Learn More About the Study Status

If you are interested in other immunotherapy studies or interested in learning about improving the efficacy of immunotherapy treatments, please email us at info@ccralliance.org .

How is the treatment given to the patients?

1. The vaccine is administered as two subcutaneous injections three weeks apart. Blood samples are also collected on these days and shipped to Yale University lab for analysis.

2. The third blood sample is collected on day 45-50 and sent to Yale University lab for analysis.

Which types of cancer might the vaccine help?

The vaccine may help with tumors that are often found to over-express EGFR or HER2 including:

• Osteosarcoma

• Hemangiosarcoma

• Transitional Cell Carcinoma

• Soft Tissue Sarcoma

• Anal Sac Carcinoma

• Mammary Carcinoma

• Pituitary Adenoma

• Glioma

• Lung Cancer

• Epithelial Nasal Carcinoma.

• Nasopharyngeal cancer

The vaccine does not help lymphoma or leukemia patients.

So far small-study data has been published for osteosarcoma and hemangiosarcoma only.

What are the enrollment criteria for the study?

Please contact the clinic to learn about the enrollment criteria and what additional treatments might be offered in conjunction with the vaccine.

Can a dog with cancer metastasis receive this vaccine?

Yes, but this will depend on the study location currently.

Researchers are particularly interested in patients with evidence of metastatic disease, and the Seattle clinic study is open to patients with metastasis.

What kind of side effects might be expected?

According to Dr. Mamula, the observed side effects have been minimal.

20-25% of dogs develop a sterile abscess, a large lump near the injection site. This is not an infection but is due to inflammation - a sign that the immune system is doing its job. It may ooze but will eventually resolve on its own without causing any discomfort to the dog. The use of warm compresses helps.

How much does the treatment cost?

The vaccine itself is free. Pet parents were responsible for the payment for exams and vaccine injections at the veterinary clinic.

Are there any published data on the vaccine’s safety and efficacy?

Yes, there have been several presentations at veterinary conferences as well as the publication of peer-reviewed papers.

A recent paper included their early clinical findings.

The team has also shared their study summaries at two veterinary conferences (ACVIM and Veterinary Cancer Society Meeting) in 2021. One of the poster submissions is shown below. And shares the survival curve for osteosarcoma patients for up to 12 months.

Canine Cancer Alliance is providing financial support to the Yale research project to facilitate additional data collection, and to investigate ways to improve responses in more dogs.

Any other information available?

Canine Cancer Alliance hosted Professor Mamula's lecture on Oct 3, 2020. The slides and recording are available here.

Professor Mamula has given several presentations at conferences for veterinarians, including at the Veterinary Cancer Society meetings in 2022. There, he shared that in addition to helping dogs with osteosarcoma, his team was observing efficacy with dogs with hemangiosarcoma. But these are very small-number studies.

Please go to this page for the most recent status and information. We try to keep this page updated.

Are dogs experiencing durable remission?

Yes. Some canine patients with osteosarcoma who had exhausted conventional options are experiencing long-term remissions.

Examples include these pups.

Codi

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 out about the vaccine trial by a Google search and brought him to Connecticut.

"The use of the vaccine resolved the metastasis, and the sign of cancer disappeared."

Codi became cancer-free and thrived for several years.

Sadly, Codi was diagnosed with another cancer - hemangiosarcoma- in his liver in August 2020, and passed away.

But he had an excellent quality of life after the vaccine-induced resolution of his pulmonary metastasis and all signs of osteosarcoma disappeared.

Codi whose bone cancer had metastasized to his lungs was cancer free two years later

Jethro

A three-year-old pup, Jethro, was diagnosed with hemangiosarcoma in March 2019. He received the vaccine treatment and is thriving with no sign of cancer.

Maggie

Maggie was battling osteosarcoma and had her leg amputated in February 2020. She was finishing her chemotherapy when her mom found out about the vaccine. Hoping for a chance to stop the cancer from spreading, she reached out to Professor Mamula, and Maggie got the vaccine shots in Aug 2020.

Maggie returns to the vet every three months for blood work and x-rays but so far, she has been cancer-free for close to 36 months (Jan 2023).

Lilly

Stitch's biological sister sister, Lilly, was also diagnosed with osteosarcoma. She received the vaccine but she did not get surgery or chemotherapy. She survived for about 12 months until the tumor metastasized to her eye.

12-month survival is impressive for a canine osteosarcoma patient who didn't receive surgery or chemo.

Many dogs responded positively to the vaccine, but there are also many dogs whose survival times did not get extended with the vaccine.

What does the survival data look like?

The preliminary survival data for patients with osteosarcoma for 360 days is shown below.

The 43 canine patients had received surgery, carboplatin chemotherapy and the vaccine. 65% of patients survived to 12 months. Without the vaccine (but with surgery and chemotherapy), 35-40% of patients survive to 12 months.

Survival data for osteosarcoma patients

We are looking forward to seeing the publication of longer-term data for osteosarcoma patients, as well as for other cancer types.

Can it help dogs with metastasis?

A small number of dogs experienced reversal of pulmonary metastasis, including Codi described above.

The chest x-ray images from one of the publications are shared below.

Red circle: lung metastasis. Lung metastases disappeared in these three dogs.

Ranger is another lucky dog.

Ranger’s dad shared this post on Facebook recently (shared here with his permission).

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From Rick Kneisel (Ranger's dad) :

“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) and 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 OSU 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.”

Ranger's metastasized tumors disappeared after the vaccine treatment

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Ranger is well and cancer-free, over three years after his metastasis was discovered.

It is not yet known what percentage of dogs with lung metastasis became long-term survivors.

How can I arrange for this vaccine treatment for my dog?

Once they obtain approval from the USDA, a new company called TheraJan is expected to manufacture the vaccine and make it available to veterinary clinics throughout the US.

Check the current study status and how to see if your dog might enroll in the trial by clicking this button.

Find out how to get the vaccine

Please sign up to be notified when new study locations open or to learn about other research insights that may help more dogs respond to immunotherapy.

You can also email us at info@ccralliance.org .

There is also a Facebook group for Yale Canine Cancer Vaccine here:

https://www.facebook.com/groups/620190395093636/?ref=bookmarks .

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Are there other immunotherapy treatments for helping canine osteosarcoma patients?

There are several new treatments and studies that may help osteosarcoma patients, including a new ‘personalized’ immunotherapy from ELIAS Animal Health. You can read more about ELIAS immunotherapy treatment here.

A recent study at Tufts University and Colorado University Vet School also showed that a combination of oral drugs can be used to help dogs with osteosarcoma and other types of cancer. The drug combination included propranolol, high-dose losartan and toceranib.

Other immunotherapy treatments for osteosarcoma patients are summarized in this article.

Our gratitude to Amee Gilbert and Tira C. for reviews and inspiration!

Please consider giving. The Yale vaccine study is made possible by donations from pet parents.

Donate to support this research

References

Doyle HA, Koski RA, Bonafé N, et al. Epidermal growth factor receptor peptide vaccination induces cross-reactive immunity to human EGFR, HER2, and HER3. Cancer Immunol Immunother. 2018;67(10):1559-1569. doi:10.1007/s00262-018-2218-9

2.

Doyle HA, Gee RJ, Masters TD, et al. Vaccine-induced ErbB (EGFR/HER2)-specific immunity in spontaneous canine cancer. Translational Oncology. 2021;14(11):101205. doi:10.1016/j.tranon.2021.101205

Journal of Veterinary Internal Medicine 2021 ACVIM Forum Research Abstracts

Veterinary Cancer Society Annual Conference Oct 2022.

Veterinary Cancer Society Mid-Year Conference Apr 2022.