Cancer is an extremely common disease in nearly all living things, and it's one of the leading causes of death in dogs. As such, various forms of cancer are frequent sights in veterinary practices around the world.
Cancer is, unfortunately, extremely complex. It's not an external invader like infections, and it's not as simple as damage like an injury; cancer is an umbrella term for a variety of different expressions of damage to DNA, causing uncontrolled replication of certain types of cells. Since these cells don't function properly, they grow unchecked, causing tumors, health problems, and more.
The two biggest challenges with treating cancers are:
Each different cancer responds differently to different kinds of treatments, so there's no singular "cure" for "cancer"; just treatments for specific kinds.
Cancer cells are, more or less, just cells from the body, meaning they are often ignored by the immune system and allowed to replicate unchecked. This is called "immune tolerance" and is one of the key challenges of all cancer treatments.
Among the many different kinds of treatments for cancer being developed over the last decades with modern medical advances, that second point is becoming critical. A whole class of treatments called immunotherapies are increasingly being developed and showing great promise for treating cancers of various types, including both human and canine cancers.
The Yale EGFR/HER2 vaccine is one such potential treatment. What is it, is it available, how does it work, and what do you need to know about it as a vet who sees patients with cancer in varying forms and stages? Read on for our rundown.
What is The Yale EGFR/HER2 Cancer Vaccine for Dogs?
The Yale Vaccine is a form of immunotherapy meant to treat a handful of specific canine cancers, but primarily canine osteosarcoma. It's currently undergoing trials in ten locations throughout the United States, though as time goes on and it is more broadly proven to be safe and effective, additional locations can be added and broader trials performed until it can be approved for clinical use.
Traditional treatments for canine osteosarcoma involve amputation of the affected limb, chemotherapy, and radiation therapy. These can be immense surgeries that carry their own risks, and treatments are often only moderately effective.
For an idea of early results, in a study of 43 patients, those given chemotherapy and surgery survived to 12 months at a 40% rate; those given surgery, chemo, and the vaccine survived to 12 months at a 65% rate. (Citation here.)
As a promising new form of immunotherapy, these trials are exciting and worth watching.
The vaccine is being developed by Yale researchers Professor Mark Mamula and research scientist Dr. Hestor Doyle, both immunologists, and their research team.
What is Immunotherapy and How Does it Work?
The term "vaccine" is appropriate for immunotherapy. While we traditionally think of vaccines as preventative, they can also be treatments.
The immune system is a carefully-balanced system involving numerous processes in the body. Under normal circumstances, this system patrols the body to find anything out of the ordinary or out of place. This includes external invaders like bacteria and viruses, as well as internal issues like damaged cells. When the immune system detects these issues, it mobilizes specialized attack cells to neutralize the unusual cell and get rid of it.
When the immune system goes wrong, all sorts of things can happen. Allergies are an immune system reaction. Autoimmune diseases are caused when the immune system triggers on something it shouldn't. And, of course, the immune system can only prepare to fight something it has been exposed to.
Immunotherapies and the vaccines that compose them are, essentially, neutralized examples of what the immune system should be fighting. Exposing the body to that example helps train the immune system to identify and fight those cells, which can include anything from diseases like influenza to, now, cancer cells.
All of this is a simplification. For a more detailed explanation of how the immune system works with regard to cancer and how cancer can be fought with immunotherapy, this resource is excellent. While it's focused on human cancers, the general information still applies to dogs and other animals as well.
What is EGFR/HER2?
Cancers, including canine osteosarcoma, can be identified by their mutations. In the case of the cancers addressed by the Yale vaccine, the mutation is to two proteins: EGFR and HER2. EGFR is Epidermal Growth Factor Receptor, and HER2 is Human Epidermal Growth Factor 2.
Normal cells have a few of these receptors. Cancerous cells mutate and produce an overabundance of these proteins and receptors.
The more there are, the more aggressive and difficult to treat the cancer tends to be, resulting in poorer prognoses.
"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." – Canine Cancer Alliance.
The Yale vaccine is meant to help the immune system identify and fight off any cells with an overabundance of these proteins, which are typically cancerous.
What Canine Cancers Might the EGFR/HER2 Vaccine Treat?
Many different forms of cancer are characterized by an overabundance of EGFR and HER2, as well as other forms of HER like HER3 and HER4. As mentioned in the quote above, the vaccine includes these for broader-spectrum coverage.
The greatest focus in terms of canine cancers being addressed by this vaccine is on canine osteosarcoma, with a secondary focus on hemangiosarcoma. It may have promising results for other cancer types as well, but those are the two most frequently represented in the trials.
Other cancers that express EGFR/HER2 abundance include transitional cell carcinoma, soft tissue sarcoma, anal sac carcinoma, mammary carcinoma, pituitary adenoma, glioma, lung cancer, epithelial nasal carcinoma, and nasopharyngeal cancer. So far, no definitive results have been published with regard to the Yale vaccine's efficacy for these cancers, however.
Unfortunately, this vaccine does not target or affect lymphoma or leukemia.
What Results Might be Expected from the Vaccine?
While this vaccine is far from a guaranteed cure, it shows promise in improving the outcomes and efficacy of cancer treatments in dogs suffering from these cancers.
Some dogs see partial remission after the vaccine. Others see a reversal of metastatic disease. Some have their cancer's progress slowed or halted but not reversed. Various factors that cause these differences in results are still ongoing. The vaccine may also be a viable option in cases where surgery, chemotherapy, radiation, or more than one of those are not available.
Results, of course, vary, but initial study results are promising, so the study is being expanded periodically. Some dogs see short-term improvement, some see long-term improvement, and a few experience total remission. More study is ongoing to identify what factors lead to the most promising outcomes and how to encourage them.
What is the Status of the Yale EGFR/HER2 Vaccine?
Currently, the vaccine is limited by production capacity and has not yet been approved for full development and distribution. The current phase of the study is meant to build the body of evidence to proceed to that next step. As such, the availability of the vaccine is limited to just ten locations throughout the USA and is limited to specific candidates at those locations. More on whether or not a dog qualifies and how to enroll them later.
As of this writing, this release from July 6, 2023, is the most recent update on the study. For the most updated information, check this page.
Does the EGFR/HER2 Vaccine Have Side Effects?
Side effects have thus far been minimal.
From the researchers:
"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."
Fortunately, cancer treatments are generally much lighter on dogs than they are on humans.
Can You Enroll Your Patients in the Study?
Maybe, but the chances aren't great currently.
There are currently ten locations where the clinical study can be carried out.
Bridge Animal Referral Center in Edmonds, WA
Washington State University Veterinary Teaching Hospital in Pullman, WA
MedVet Salt Lake City in Salt Lake City, UT
MedVet Cleveland in Cleveland, OH
MedVet Pittsburgh in McMurray, PA
MedVet Cincinnati in Fairfax, OH
IVO Integrative Veterinary Oncology in Phoenix, AZ
Pacific & Santa Cruz Veterinary Specialists in Santa Cruz, CA
MedVet Chicago in Chicago, IL
MedVet Northern Virginia in Manassas, VA
If you aren't one of those facilities, you will have to refer your patients to one of them for a chance at being in the study. You may also be able to apply to join the study, but you'll need to reach out to the study team directly to discuss that option.
Unfortunately, the capacity to treat more dogs is limited, as there's currently very little of the vaccine being manufactured. Currently, participating veterinary hospitals are being asked to limit themselves to five new dogs per week added to the trial.
In order to qualify:
The patient must have a histologically-confirmed case of osteosarcoma, hemangiosarcoma, or transitional cell carcinoma. Some exceptions for confirmation may apply but are unlikely.
An examining oncologist must expect a greater than three months survival.
Metastases are not disqualifying; however, prognosis restrictions may be more difficult to reach.
The patient must not be undergoing any other immunotherapies or alternative therapies and cannot be in another clinical study. Traditional chemo and radiation are allowed.
Patients enrolled in the study are given the vaccine for free but are responsible for their own costs for the required testing, which include:
"Chest X-rays, CBC, biochemical profile, and urinalysis at baseline prior to vaccine administration. Testing completed within seven days will likely be acceptable.
Chest X-rays must be repeated at 3, 6, and 9 months.
A blood sample will be collected at each visit (baseline, day 21, day 40-50, 3 months, 6 months, 9 months) for research purposes."
There is currently no timeline for the approval or expansion of the trial, but all current efforts are going toward gaining USDA approval for greater vaccine manufacturing capability and distribution.
Advice for Vets
At Hope Vet, we understand that canine cancers can be devastating to pet owners while also being routine for vets to handle, even if they aren't exactly easy.
Our advice is this.
Do what you can for your patients. While you can refer them to one of the facilities currently offering enrollment to the clinical trial, availability is slim, and there are many candidates applying every week. It doesn't hurt to recommend, but temper expectations.
Keep an eye on the trials and watch for when broader approval is gained. This seems likely given the promising results and lack of side effects so far observed, but one never can tell until the decision is made.
Once the vaccine is more broadly available, you can consider enrolling your practice in any expanded trials that may be added; alternatively, if the vaccine is more broadly available, you can likely obtain it for your patients.
In all cases, cancer diagnoses are a time of great stress and emotion for pet owners, which means the target of that stress is often the vet. If you find the pressure is mounting or simply need a second opinion, give us a call. We can help with a variety of tricky decisions and situations for any vet, including dermatology, oncology, and even your own mental health. Simply click the "Request Consult" button above to get started.