A New Promising Combination Immunotherapy Trial: Autologous Cancer Vaccine with Immune Checkpoint Inhibitor (K9-ACV + ICI)

A new trial is evaluating a new promising combination immunotherapy and enrolling dogs diagnosed with osteosarcoma

Introduction

Canine osteosarcoma is one of the most aggressive and heartbreakingly common cancers in dogs. The standard-of-care treatment—amputation followed by chemotherapy—offers limited survival benefit and median survival time is less than a year.  

A new clinical trial led by Ardent Animal Health is investigating a promising approach that combines an autologous cancer vaccine  (K9-ACV) made from a dog’s own tumor and an immune checkpoint inhibitor peptide drug.  

This is a randomized trial with the canine patients in the control arm receiving carboplatin chemotherapy following surgery.

Here’s a summary.

1. What is the combination immunotherapy being evaluated, and how does it work?

This trial is enrolling dogs with appendicular osteosarcoma.  After amputation surgery, canine cancer patients in the intervention arm are given two-part immunotherapy designed to help the dog’s immune system recognize and attack cancer cells.  The therapy consists of an autologous vaccine, made from the patient’s tumor, and an immune checkpoint inhibitor that counters cancer’s ability to suppress the immune response.  Patients selected to be in the chemotherapy arm will receive carboplatin chemotherapy treatment. 

2. Can you provide more details?

• Autologous Killed Tumor Cell Vaccine: K9-ACV. This vaccine is made from your dog's own tumor cells after the limb amputation. The tumor cells are UV-radiated to cause cell death, which creates new antigens (abnormal proteins) that the immune system can recognize. A primary adjuvant called CPG ODN is added, which mimics a bacterial adjuvant and is designed to stimulate beneficial immune responses by promoting the release of cytokines like interleukin 2 and interferon gamma. The goal is to excite the immune system to recognize and kill cancer cells.

• Novel Checkpoint Inhibitor (CD200AR-L peptide): This peptide targets the CD200 receptor, which is part of an immune checkpoint pathway. Normally, when CD200 binds to its receptor (CD200R), it suppresses the immune system by reducing cytokine production and can even recruit immune-suppressor cells. The CD200AR-L peptide works by blocking this inhibitory pathway. This action is intended to:

  • Promote good co-stimulatory molecules (like CD80).

  • Produce beneficial cytokines, fostering a strong immune response.

  • Downregulate other immune checkpoints such as PD1, PDL1, and CTLA4. Essentially, it aims to block the "don't eat me" signal that cancer cells use to evade the immune system, allowing the T-cells to identify and kill the tumor cells.

3. Has this treatment been evaluated before?

Yes, components of this treatment have been tested in other dogs and animals:

• The K9-ACV vaccine (without the CD200 peptide) has been safely used in over 1,000 dogs. Ardent Animal Health, the company leading the trial, has internal data showing over 1,500 dogs vaccinated with vaccine alone.

• Specifically for osteosarcoma, Ardent has treated approximately 50 dogs with vaccine alone, with an observed median survival time close to nine months.

• The CD200 peptide (CD200 ARIRL) was tested in a canine glioma (brain tumor) model at the University of Minnesota. In this study, dogs that received surgery along with a tumor lysate vaccine and the CD200 peptide showed significantly improved survival compared to those who received surgery and vaccine alone, with a median survival time of 13 months, which is considered remarkable for canine glioma. This positive data led to the CD200 peptide moving into human glioma clinical trials.

  
  

4. What are the possible benefits?

With today’s standard-of-care therapy for osteosarcoma (surgery + chemotherapy), the vast majority of patients end up with metastasis in lungs.  This new therapy aims to match or extend the disease-free interval (time without detectable cancer) without chemotherapy and improve quality of life. The hope is

• Delay or prevent metastasis.

• Avoid side effects and systemic toxicity associated with chemotherapy.

• Potentially extend survival beyond 9 months, engaging immune memory.

  
  

5. What are the possible side effects of the therapy?

Expected side effects are generally transient and mild.

• Local: Redness or swelling at the injection site.

• Systemic: Mild fever, lethargy, or reduced appetite.

• Rare: Anaphylaxis or autoimmune-type inflammation.

• Brain inflammation was seen in glioma studies, but not expected in osteosarcoma due to its low risk of brain spread.

  
  

6. Will my dog still be able to receive other treatments during or after the trial?

• During: No concurrent chemo, corticosteroids, NSAIDs, or immunotherapy

• After:

  • Dogs in the chemo arm can switch to immunotherapy if there is cancer progression (compassionate use)

  • Immunotherapy-arm dogs may not benefit from switching to chemo if cancer recurs

    
    

7. Is this treatment targeted for a specific cancer type, stage, or breed?

Inclusion is limited to:

• Dogs >1 year old and >20 kg (44 lbs)

• Diagnosed with appendicular osteosarcoma (limb tumors)

• No metastasis

  
  

8. How often will we need to visit the clinic or hospital?

The frequency of visits depends on which group your dog is assigned to:

• Screening: All participating patients will undergo standard pre-enrollment screening visits.

• Amputation: After passing the screening, your dog will undergo limb amputation.

• Immunotherapy Group (K9-ACV):

  • After amputation, your dog will receive an intradermal injection of the checkpoint inhibitor (CD200AR-L).

  • You will then return to the study site 24 hours later for the vaccine administration (which includes a second dose of the checkpoint inhibitor simultaneously).

  • These vaccine and checkpoint inhibitor administrations will be given every 3 weeks for a total of 3 treatments.

  • Following the treatments, patients will return for follow-up visits at 4, 6, and 8 months after the initial vaccine administration.

• Chemotherapy Group (Carboplatin):

  • Patients in this group will be treated every 3 weeks for a total of 4 treatments.

  • Similar to the immunotherapy group, patients will return for follow-up visits at 4, 6, and 8 months after initial chemotherapy treatment.

    
    

9. What procedures, tests, or scans will my dog undergo during the trial?

Your dog will undergo various procedures, tests, and scans throughout the trial:

• Pre-enrollment Screening: This involves a physical exam, blood work, chest x-rays, and an abdominal ultrasound.

• Limb Amputation: All enrolled dogs will undergo limb amputation.

• Vaccine Production (for Immunotherapy Group): For dogs in the immunotherapy arm, your dog's amputated limb will be sent to Ardent Animal Health to manufacture the autologous vaccine from the tumor cells. This process takes approximately 3 to 4 days.

• Treatment Administration:

  • Immunotherapy Group: Dogs will receive intradermal injections of the checkpoint inhibitor and the autologous vaccine. These are described as tiny pricks, like a TB test, and not deep intramuscular or intravenous injections. The vaccine is also administered over draining lymph nodes.

  • Chemotherapy Group: Dogs will receive carboplatin treatments.

• Monitoring During Treatment: The sources imply monitoring during treatment periods, but specific tests are highlighted for post-treatment.

• Follow-up Monitoring (for both groups): At the 4, 6, and 8-month follow-up visits, your dog will undergo a physical exam, blood work, and chest x-rays to check for metastasis.

• Quality of Life Assessment: Quality of life will be assessed using specific criteria adapted from a geriatric oncology guide.

• Adverse Event Monitoring: Adverse events will be graded using the Veterinary Cooperative Oncology Group (VCOG-CTAEv2) scheme.

  
  

10. Will my dog be assigned to a treatment group randomly or guaranteed to get the new therapy?

Your dog will be assigned to a treatment group randomly.

• The study uses a 3 to 1 randomization scheme. This means that for every one dog assigned to the standard-of-care chemotherapy group, three dogs will be assigned to the new K9-ACV immunotherapy arm.

• This randomization is a "modified part contemporaneous part historical control" approach. While 45 dogs will be in the immunotherapy arm, the control group will consist of 15 prospective dogs and 157 historical controls, making the total control group 172 dogs.

The study investigators and owners are "masked," meaning they are blinded to which specific treatment the dog is receiving, to minimize bias. 

11. How long does it take for the therapy to start working (if it works)?

• Vaccine creation takes ~3–4 days post-surgery

• Therapy includes 3 treatments over 6 weeks

• Unlike chemotherapy, immunity builds over time

• Dogs are monitored at 4, 6, and 8 months post-treatment for remission status

  
  

12. If the treatment is effective, can I continue it after the trial ends?

• Ardent may save additional vaccine doses for possible boosters

• Access to CD200 peptide post-trial is uncertain and likely depends on future approvals

• Long-term follow-up plans are not guaranteed but are being explored

13. What are the eligibility criteria for my dog to participate?

• Age and Weight: Your dog must be at least 1 year of age and weigh 20 kilograms (approximately 44 pounds) or more.

• Health Status: Your dog should be in good general health, with the exception of appendicular osteosarcoma.

• Diagnosis Confirmation: The diagnosis of appendicular osteosarcoma, Stage IIB, must be confirmed by cytologic and/or histologic evaluation.

• Vaccine Viability: It must be possible to produce a viable vaccine from your dog's tumor. This is a crucial step, as some tumors might be too necrotic or not have enough viable cells for vaccine production.

• No Prior Treatment: Your dog must not have received concurrent or previous therapy (within 30 days) with immune-modulating drugs such as cyclosporine, Apoquel, Cytopoint, or prednisone, or any chemotherapy. Dogs who have received prior chemotherapy, radiation therapy, immunotherapy, or bisphosphonates for their osteosarcoma are excluded.

• NSAID Restriction: Your dog should not have received non-steroidal anti-inflammatory drugs (NSAIDs) less than three days before immunization with the investigational veterinary product, as NSAIDs can interfere with the innate immune system's activity.

• Other Conditions: Your dog should not have any uncontrolled medical condition likely to disrupt the study's intent.

• Reproductive Status: Your dog must not be known to be pregnant, likely to become pregnant, lactating, or intended for breeding during the study.

• Study Participation: Your dog cannot be participating in another therapeutic study or be unavailable for the duration of this study

Exclusion criteria:

• Prior treatment (chemo, radiation, immunotherapy)

• NSAID or corticosteroid use near vaccine time

• Pregnancy, lactation, or breeding intent

• Other major uncontrolled diseases

  
  

14. Will my dog be sedated or anesthetized for any part of the trial?

• Yes: For limb amputation, general anesthesia is required for limb amputation

• No: Immunotherapy injections are intradermal (like TB tests) and require no sedation

  
  

15. Where are the hospitals participating in this clinical trial?

• Primary Study Location: University of Illinois

• Additional Study Locations: Maine Veterinary Medical Center, University of Wisconsin, BluePearl Lafayette, BluePearl Tacoma, BluePearl Pittsburgh, Veterinary Cancer Group of Orange County, South Carolina Veterinary Specialists and Emergency Care, CARE Center Cincinnati, Metropolitan Vet Hospital, Peak Veterinary Referral Center, Colorado Animal Specialty and Emergency, VSH North County, Mission Veterinary ER and Specialty, Massachusetts Vet Referral, Metropolitan Vet Hospital Cleveland, Southeast Veterinary Oncology & Internal Medicine

  
  

16. What happens if my dog gets worse during the trial—can we withdraw?

• Yes, participation is voluntary. Owners can withdraw at any time

• If the disease progresses:

  • Chemo group dogs may switch to immunotherapy (compassionate use)

  • Immunotherapy group dogs are not typically offered chemo afterward

• Data collected until withdrawal is still valuable to research

  
  

17. Are there any costs I’ll need to pay, or is everything covered by the study?

This is a partially funded study.

• Ardent covers:

  • Vaccine production

  • Checkpoint peptide

  • Some trial-related follow-up tests

• You may be responsible for:

  • Amputation surgery

  • Non-study veterinary care

    
    

Please discuss with your trial coordinator—some sites may offer subsidies.

18. What is an immune checkpoint, and how do immune checkpoint inhibitors work?

• Immune checkpoints are natural brakes that keep the immune system from overreacting

• Cancer cells hijack these brakes to avoid detection

• Checkpoint inhibitors (like anti-PD-1 or CD200AR-L peptide):

  • Block these inhibitory signals

  • Enable T-cells to kill tumor cells more effectively

Currently, one other immune checkpoint inhibitor (PD-1 ICI) called Gilvetmab is conditionally approved and available to veterinary oncology clinics in the US.

19. What makes the CD200 pathway a compelling target in canine cancer?

• CD200 is a suppressive molecule found on many cancer cells

• When CD200 binds its receptor (CD200R), it:

  • Shuts down beneficial cytokine production

  • Attracts regulatory cells that silence anti-tumor responses

• CD200AR-L peptide blocks this signal, resulting in:

  • Stronger immune activation

  • Downregulation of PD-1, PDL1, and CTLA-4

  • Enhanced immune memory

    
    

20. Could this therapy help other dogs in the future, even if it doesn’t help mine?

Absolutely. By participating, your dog contributes to helping future canine patients with osteosarcoma, and also possibly help benefit children with osteosarcoma. In the future, if therapy is approved, it may help dogs with many different cancer types, not just osteosarcoma.

Get Your Free Immunotherapy Guide

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Learn more:

• A New Combination Immunotherapy: Webinar

• AVMA clinical trial description

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• Surprising Findings from 2024

• New Canine Cancer Screening Tests

Questions? Email us at info@ccralliance, and we'll get back to you as soon as we can!

Canine Cancer Alliance is a non-profit organization supporting research for canine cancer cures.

All information on the Canine Cancer Alliance website is for educational purposes only. It is not intended to be a substitute for professional veterinary advice.

Always seek guidance from your veterinarian with any questions regarding your pet’s health and medical condition.