Canine Sarcoma: An Overview of Cancer Immunotherapy

Cancer immunotherapy is starting to offer new hope to families of dogs with sarcoma.

In this article, we explore the potential benefits and other key aspects of cancer immunotherapy treatments that are becoming available to canine patients.

What is cancer immunotherapy?

Cancer immunotherapy is a type of cancer treatment that uses the body's own immune system to fight cancer.

Unlike conventional therapies that directly try to kill cancer cells, immunotherapy targets the immune system and its interaction with cancer cells. When successful, an immunotherapy treatment can restore the capacity of the immune system to recognize and reject cancer.

Here are some essential things to know about cancer immunotherapy for our pups.

Gus and Hanako were diagnosed with osteosarcoma and hemangiosarcoma in 2016. Conventional treatments gave Gus an extra year. No treatment option was available for Hanako's advanced hemangiosarcoma.

Different Immunotherapy Treatments

There are different types of immunotherapy treatments in various stages of development for canine patients. Some have been fully approved for veterinary use by the USDA or the FDA, whereas others are experimental therapies and available only through a clinical trial.

The different types of immunotherapy treatments include:

• Cancer Vaccines

Injections or infusions are given to stimulate the immune system against certain cancer-associated targets. For example, EGFR/HER2 vaccine consists of a simple peptide chain and is effective at training the immune system to attack many types of cancer cells that over-express EGFR and HER2 proteins. Torigen vaccine - available commercially today - is created from a patient's tumor cells and targets a unique set of antigens associated with the patient.

• T-Cell Transfer Therapy (also called adoptive cell therapy)

Cancer-fighting T-cells are taken from a patient, modified/activated, and amplified in the laboratory in-vitro, and given back to the patient. Elias Animal Health Immunotherapy has conditional approval from the USDA and is today available for dogs with osteosarcoma. CAA is supporting a CAR-T therapy targeting B7H3 receptors at a trial at the University of Illinois.

• Nonspecific Immunotherapies

Nonspecific immune-modulating agents stimulate the immune system in a general way, rather than by targeting specific proteins or receptors. They include cytokine therapies as well as drugs derived from bacteria. Immunocidin is an example of nonspecific immunotherapy. Originally approved for the treatment of mammary tumors, Immunocidin is being studied for efficacy in treating other cancer types. IL-12 cytokine therapy for dogs with soft tissue sarcoma is another study supported by CAA.

• Immune Checkpoint Inhibitor Drugs (also called Checkpoint Blockade Drugs)

Cancer cells have the ability to turn off immune activity by generating molecules that target checkpoint receptors. But Immune Checkpoint Inhibitor drugs can block cancer's immunosuppressive signaling. Multiple checkpoint inhibitor drugs have been approved for human patients including those that target PD-1, PDL-1, and CTLA checkpoints.

For example, in a highly publicized case, former president Jimmy Carter was successfully treated for melanoma that had spread with the help of a checkpoint inhibitor drug. Checkpoint inhibitors for dogs are in development by several research groups and are expected to be available very soon.

Former President Jimmy Carter had metastatic melanoma. But with the help of checkpoint inhibitor treatment, he became cancer free.

• Repurposed Oral Drugs

One of the most exciting recent developments is the discovery that widely available drugs that were not originally developed for cancer can have strong anti-cancer immune-modulating effects. These repurposed drugs are safe, widely available, and inexpensive. Examples include hypertension drugs propranolol and losartan. These and other immunomodulatory strategies that hold promise will be described in more detail in future articles.

Potential Benefits

The potential benefits for both canine and human patients include:

• Precision: Immunotherapy can be more precise in its action, specifically targeting cancer cells without affecting healthy cells. That means that in contrast with chemotherapy and radiation therapy, healthy cells are not harmed and side effects may be mild.

• Long-Survival: Immunotherapy can have long-lasting effects because it educates the immune system to recognize and destroy cancer cells. This means that the immune system could potentially continue to protect against cancer long after treatment has ended, reducing the risk of recurrence. Immunotherapy may also help dogs with metastatic cancer.

• Tackling Resistant Cancers: Too often, cancer becomes resistant to conventional therapies. Immunotherapy can be a valuable treatment option in these cases, providing an additional method of attacking the cancer.

Ranger (right) had osteosarcoma that spread to his lungs. He became cancer-free with the help of EGFR/HER2 vaccine.

Risks and Side Effects

Like any medical intervention, cancer immunotherapy carries certain risks and possible side effects. The specific risks and side effects depend on the type of immunotherapy used and the individual patient. Some of the slightly more common side effects include lethargy and fatigue, loss of appetite, injection site swelling, and fever. (But the side effects such as swelling and fever may be a sign that the immune system is responding). Sometimes, the tumor may appear to grow due to an increase in white blood cells infiltrating the tumor microenvironment. This is called pseudo-progression.

More serious side effects or adverse events might include cytokine storms that may lead to organ damage, auto-immune disorders, and deleterious long-term effects. There have not been enough studies on canine immunotherapy patients to understand the full range of risks, so it is extremely important to find out from the veterinary clinic what the risks are for the particular immunotherapy.

Immunotherapy Treatment Efficacy

In contrast to conventional treatments, a fraction of canine patients treated with immunotherapy has a chance of long survival.

For example, a notable fraction of the dogs that received the HER2 targeting listeria vaccine developed at the University of Pennsylvania became long-term survivors, living well over 400 days. A 'long tail' can be seen in the survival curve.

HER2/neu targeting listeria vaccine survival curve.

Slightly less than half of the dogs who participated in Elias Animal Health's pilot T-cell transfer therapy trial have also been able to enjoy long remission from osteosarcoma, as seen by a long tail in the survival curve below.

Elias Animal Health's T-cell transfer therapy combined autologous vaccination and IL-2 infusion helped dogs become long survivors.

Is immunotherapy right for my dog? Where can we get the treatment?

For human patients, immunotherapy has demonstrated significant success in treating various types of cancer, including melanoma, lung cancer, bladder cancer, and certain types of leukemia and lymphoma. For canine patients, there is only a small number of fully approved immunotherapy treatments for oral melanoma and mammary tumors. Many more experimental immunotherapy treatments are being evaluated as part of clinical trials.

Whether immunotherapy is right for you depends on several factors, including the type of cancer your dog has and the stage. Your veterinary oncologist can provide advice based on your specific circumstances.

Based on the AVMA clinical trials database and other public sources, the list of immunotherapy treatments and locations are summarized on the following pages:

• Immunotherapy for Canine Osteosarcoma Patients

• Therapies for Hemangiosarcoma Patients

• Therapies for Soft Tissue Sarcoma Patients

Please note that the lists were compiled by CCA volunteers and last updated on July 12, 2023. Please rely on your veterinarian for the best, most up-to-date recommendation, as there may be other options that might have been overlooked.

Today's cancer immunotherapy doesn't work for everyone

While seeing a long survival tail is extremely exciting, today's immunotherapy works for a fraction of patients.

After leg amputation and chemotherapy, Walden received the experimental EGFR/HER2 vaccine developed at Yale. Sadly, he passed away several months later due to metastatic osteosarcoma.

Here is 12-month survival data published for the EGFR/HER2 vaccine treatment that had been given to canine osteosarcoma patients.

At 12 months, it helped roughly 60% of dogs participating in the study. This percentage is greater than that for dogs receiving conventional treatment of surgery and chemotherapy (35-40% survival at 12 months) , but still, many dogs did not respond to the therapy.

Two questions surrounding immunotherapy are why do some dogs respond to immunotherapy while others don't, and why do some dogs initially respond but develop resistance over time? These are the key questions that researchers are focusing on so more lives can be saved.

Codi's osteosarcoma had spread to his lungs. But he became cancer-free and lung nodules disappeared after receiving EGFR/HER2 vaccine therapy. He was a happy, active pup for three years but sadly, Codi passed away from hemangiosarcoma.

Molly loved to swim, even after her leg amputation. She was one of the first dogs to respond positively to a new immunotherapy using repurposed drug Losartan. One of her lung nodules even disappeared. But sadly, the cancer developed resistance to her therapy. (Source: U of Colorado)

Raising the tail: how to improve efficacy?

The interactions between the immune system and cancer cells are continuous, dynamic, and evolving from the initial establishment of a cancer cell to the development of metastatic disease. As the molecular mechanisms of resistance to immunotherapy become better understood, actionable strategies to help more dogs respond to the treatment can be developed.

One promising approach is to use combination therapy.

With human patients, a checkpoint inhibitor drug, Ipilimumab, was helping a small subset of patients with melanoma become long-term survivors. (Below in blue). When another checkpoint inhibitor targeting different checkpoint receptors was added, there was a dramatic increase in patient response (red line).

In a large human patient trial, two immune checkpoint inhibitors were combined to help many more patients respond to immunotherapy and become long survivors.

Checkpoint inhibitor drugs are not yet widely available for canine patients. But combination treatments may still be possible with multiple experimental immunotherapy treatments (as well as conventional therapies) to boost the response and to raise the survival tail.

This will be the topic of the next articles, where we will share possible strategies for using repurposed oral drugs, dietary modification, and other actions that may safely help more dogs respond to immunotherapy.

Questions? Feel free to reach out the Canine Cancer Alliance at info@ccralliance.org.

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All information provided by the Canine Cancer Alliance website is for informational purposes only. It is 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 and medical condition.