CANCER IMMUNOTHERAPY FOR OUR PETS
Immunotherapy treatments have been the most effective in treating difficult cancers in humans, alongside or in lieu of traditional treatments options such as surgery, radiation, and chemotherapy. Below we summarize types of immunotherapy, and list examples of treatments developed for dogs. This is followed by a review of available immunotherapy treatments. The final sections review where and how to search for clinical trials for emerging treatments for your pet’s cancer, and links additional helpful literature reviews and resources for those wishing to better understand immunotherapies.
Types of Immunotherapies
-
Preventative vaccines – These injections attempt to train the immune system of cancer-free dogs to recognize and immediately attack common abnormal proteins associated with a variety of cancers.
- The Vaccination Against Canine Cancer (VACCS) – This is a preventive vaccine undergoing clinical trials. It is a combination of about 30 abnormal proteins found on the surface of common canine cancers (lymphoma, osteosarcoma, hemangiosarcoma, and mastocytoma). The aim is to develop memory T-cells that react when a tumor develops and the immune system encounters the protein. https://www.csuanimalcancercenter.org/vaccination-against-canine-cancer-study/
-
Therapeutic vaccines – These injections treat existing cancers. They take advantage of the dog’s natural defenses by stimulating the immune system to recognize and attack cancer cells. These injectable drugs take advantage of a variety of technologies, including monoclonal antibodies (more below) and DNA-based.
- Oncept (DNA-based) vaccine for Canine malignant melanoma
-
Autologous cancer vaccines – Injections created from immune cells extracted from the patient and enhanced in the lab to better target cancer cells. Pet parents pursuing this route should determine the steps to take prior to tumor removal to prepare appropriately for sending the tumor specimen to the appropriate laboratory.
- Elias, Therajan, Torigen, K9-ACV (some of these use multiple technologies)
-
Oncolytic Viruses/Bacteria – these viruses can initiate a similar immunotherapy response as vaccines, and may also have a direct cytolytic effect.
- Immunocidin
-
Monoclonal Antibodies (MABs) and Immune Checkpoint Inhibitors (ICIs) – MABs work by mimicking naturally-produced antibodies: they recognize and bind to specific proteins on cancer cells, blocking them from functioning or flagging them for destruction by the immune system. Only a small number of canine cancer antigens are known, there is limited progress in this field. However, Vetigenics (co-founded by Nicola Mason and Don Siegel of PennBet and Adriann Sac) (vetigenics.com) has launched a platform that helps rapidly develop canine antibodies for therapeutic purposes. Vetigenics has started announcing clinical trails as of November 2023, including anti-CL4 monoclonal antibody (VGS-001) and anti-canine PD1 (VGS-002) for canine bladder cancer. https://pci.upenn.edu/first-canine-patient-receives-vetigenics-fully-canine-anti-ctla4-monoclonal-antibody/
- Tanovea, Glivetmab
- CD20 antibodies have been developed by Arantana and Elanco, including “Blontress, AT-004” which was licensed by the USDA for the treatment of large B cell lymphoma, but there are questions about is efficacy. Aratana also developed “Tactress, AT-005” for canine T-cell lymphoma. There are similar questions about efficacy, but Tactress is still available to veterinary oncologists despite no per-reviewed clinical evidence or efficacy. Elanco developed another Anti-CD20 antibody; this is still under research.
- Others, including tumor environment modulations, cytokines, etc.
Available Immunotherapies
Therajan
- https://therajan.com/joomla/
- Find a clinic: https://therajan.com/joomla/index.php/find-a-clinic
- FAQ: https://therajan.com/joomla/index.php/faqs
- For cancers that overexpress the proteins epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) (including colorectal cancer, breast cancer, and osteosarcoma), they developed a new vaccine called Therajan. According to the study, EDGFR peptide vaccinated dogs developed anti-EGFR/HER2 antibodies, and those antibodies and T-cells infiltrate tumors. Vaccinated dogs with osteosarcoma had tumor regression and increased survival. https://pmc.ncbi.nlm.nih.gov/articles/PMC8379704/
- Safety/efficacy not yet established by USDA; for use under supervision/administration of a licensed veterinary oncologist.
- Eligible cancers are EGFR/HER2 expressing cancers, including osteosarcoma, hamngiosarcoma, transitional cell carcinoma. There are clinical trials for these first three. Other EGFR/HER2 expressing cancers also include some lung cancers, anal sac carcinoma, breast and colon cancers. This is not a complete list; its action is being studied in numerous other cancers. Lymphomas and leukemias are ineligible because they do not express EGFR/HER2.
ELIAS Cancer Immunotherapy (ECI)
- https://eliasanimalhealth.com/
- Find a clinic: https://eliasanimalhealth.com/available-locations/
- FAQ: https://eliasanimalhealth.com/pet-owners/faqs/
- For dogs with newly-diagnosed appendicular osteosarcoma, no signs of metastatic disease, and in generally good health. Limb cannot be amputated prior to evaluation by ECI-trained oncologist. If ECI selected, limb will be amputated and tumor tissue collected. This treatment vaccinates a dog with its own cancer cells to produce and immune response. Personalized T cells are then obtained from the patient and reinfused into the patient to kill the cancer.
- https://eliasanimalhealth.com/wp-content/uploads/2022/08/ELIAS-Animal-Health-ECI-Technical-Summary-July-2022-1.pdf
- Eligible cancers: Osteosarcoma
Torigen
- https://www.torigen.com/
- Veterinarians order the kit online
- FAQ: https://www.torigen.com/for-pet-owners
- An autologous cancer vaccine comprised of deactivated tumor cells combined with a medical-grade adjuvant, particulate small intestinal submucosa. Some studies have shown such treatments decrease cancer tumor malignancy and metastasis.
- Eligible cancers: A vaccine can be made from any solid tumor, so many cancer types are eligible. Mast cell, hemangiosarcoma, etc.
Tanovea
- https://my.elanco.com/us/tanovea
- Find a clinic: check oncology centers near you for availability
- FAQ: https://www.elancolabels.com/us/tanovea-client-information-sheet, https://www.dogcancer.com/articles/drugs/tanovea-rabacfosadine-chemotherapy/
- About: The monoclonal antibody active ingredient rabacfosadine is a compound that accumulates in lymphoid tissues. Once inside, it inhibits certain DNA polymerases which result in DNA synthesis arrest, interrupting cell division and inducing programmed cell death. While not as effective as the standard protocol, CHOP, it can be used as a rescue protocol for CHOP, standalone treatment, or in combination with chemoterhapy drugs.
- Eligible cancers: lymphoma
Oncept
- https://bi-animalhealth.com/pets/canine/products/therapeutics/oncept
- Find a clinic: check oncology centers near you for availability
- FAQ: https://toegrips.com/melanoma-vaccine-dog/ (none available from manufacturer)
- USDA conditionally approved in 2007 for locally-controlled stage II or III oral malignant melanoma. Oncept is a xenogenic DNA vaccine; dogs receiving it can develop anti-human tyrosinase-specific humoral and cellular responses that may cross-react with canine tyrosinase to hopefully control micrometastatic melanoma progression. Oncept has been used in an off-label manor for malignant melanomas at other sites than oral (toe, eye), and in dogs at stage I, and in other species.
- Eligible cancers: Melanoma, especially oral malignant melanoma
Glivetmab
- https://www.merck-animal-health-usa.com/species/canine/products/gilvetmab-product-overview
- Find a clinic: check oncology centers near you for availability, it can be ordered by oncologists for anyone they think it may helps
- FAQ: https://www.merck-animal-health-usa.com/offload-downloads/gilvetmab-program-faqs
- A monoclonal antibody/immune checkpoint inhibitor that targets PD-1 on T cells.
- Eligible cancers: Conditionally licensed by the USDA to treat dogs with stage I to III mast cell tumors and stage II to III malignant melanomas. Currently given by IV infusion, but there are studies looking at intratumoral injection. There are a variety of studies looking at glivetmab especially adjuvant to other treatments (Alias, radiation, Toceranib, EGFR/HER2, and other chemotherapies, etc.)
- It has also been found that FMT can improve anti-PD-1 efficacy in unresectable or metastatic solid cancers in humans (and even turn non-responders into responders) – raising the question, can canine FMT tablets help? (We don’t know yet.)
K9-ACV
- https://ardentanimalhealth.com/canine-cancer/
- Find a clinic: https://ardentanimalhealth.com/find-a-vet/
- FAQ: https://ardentanimalhealth.com/canine-cancer/
- An analogous vaccine that develops an injectable treatment created from the dog’s own tumor tissue.
- Eligible cancers: Vaccines can be made from solid tumors, so many types are eligible.
Stelfonta
- Website: https://stelfonta.com/ (https://vet-us.virbac.com/stelfonta)
- Find a clinic: https://us.virbac.com/stelfonta-find-a-vet
- FAQ: https://stelfonta.com/resources/
- About: Stelfonta is injected directly into the tumor to treat non-metastatic mast cell tumors in dogs. Stelfonta stimulates the actiony of enzymes called protein kinase C which regulate cell growth and survival processes. The blood supply of the tumor is removed and the immune system is stimulated to heal the cancer site. Stelfonta injection must be carefully managed by a veterinarian as there can be significant tissue necrosis and wound transformation during treatment.
- Eligible cancers: Mast cell tumors of all grades that have not yet metastasized, that are no more than 10cm3, and are easy to reach for injection on the surface of the dog’s skin, or below the skin if on the legs.
Immunocidin
- https://www.immunocidin.com/, http://novavive.ca/product/U.S.A./immunocidin-canine
- Find a clinic: https://www.ccralliance.org/post/immunocidin-anti-cancer-immune-system-booster Immunocidin can be ordered by veterinarians through NovaVive and administered at a regular veterinary clinic
- FAQ: https://www.immunocidin.com/downloads/Immunocidin-QandA.pdf
- About: Immunocidin is an intratumoral injection derived from mycobacteria; it is an emulsion of mycobacterial cell wall fractions which are modified to reduce their toxic/allergic effect, but retain their anti-tumor and immunomodulatory activity. This is one of the oldest treatments approved by the USDA. The vaccine stimulates the activation of cytokines and lymphocytes with anti-tumor activity. The vaccine can be used as the sole treatment, as a pre-operative treatment before surgical excision, or post-operatively to reduce the risk of metastatic disease. Prognosis is guarded for cancers that have already metastasized. Although intratumoral, the response is generalized and untreated sites may also undergo regression (http://novavive.ca/product/U.S.A./immunocidin-canine)
- Eligible cancers: Mammary tumors and mammary adenocarcinomas, particularly in dogs who are not candidates for surgery or other standard-of-care treatment, or who have relapsed or were non-responsive to prior therapy. Immunocidin has also been used in cases of osteosarcoma (https://immunocidin.com/downloads/Efficacy-MCWE-osteosarcoma.pdf) and transitional cell carcinoma bladder cancer, as well as others (see https://www.ccralliance.org/post/immunocidin-anti-cancer-immune-system-booster). See also: http://novavive.ca/uploads/products/files/immunocidin-research-summary-09-21.pdf.
Institutions to check for novel therapies/clinical trials
The largest registry for veterinary clinical trials is the American Veterinary Medical Association’s: https://veterinaryclinicaltrials.org/
Many university veterinary schools and also independent institutions conduct clinical trials on novel treatments for canine cancer. Some of the major centers are listed below, but a larger list of potential sites can be found at https://vetcancersociety.org/resources/clinical-trials/.
-
University of Pennsylvania School of Veterinary Medicine
- Clinical Trials: https://www.vet.upenn.edu/research/centers-laboratories/center/penn-vet-cancer-center/clinical-trials
- Mason Laboratory for Immunotherapies: https://www.vet.upenn.edu/research/centers-laboratories/research-laboratory/mason-immunotherapy-research/therapies-trials
- UC Davis School of Veterinary Medicine
-
Flint Animal Care Center at Colorado State University
- Clinical Trials: https://www.csuanimalcancercenter.org/current-clinical-trials/
-
Purdue University
- Clinical Trials: https://vet.purdue.edu/wcorc/clinical-trials/
-
Cornell
- Clinical Trials: https://www.vet.cornell.edu/hospitals/clinical-trials
-
MSU
- Clinical Trials: https://cvm.msu.edu/hospital/veterinarians/clinical-trials
- University of Florida
-
Texas A&M
- Clinical Trials: https://studypages.com/tamuvetmed/home/
Helpful Resources / Literature Reviews
2021 Review of Immunotherapies for Dogs https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.665784/full
https://vetgirlontherun.com/updates-canine-lymphoma-vetgirl-veterinary-ce-blog/ - Lymphoma
The Promise of immunotherapeutic strategies to advance cancer treatment in pet dogs – Aug 2024 - https://doi.org/10.2460/javma.24.08.0532
https://www.youtube.com/watch?v=xP-JL27i6N0 – webinar from Canine Cancer Alliance on Glivetmab
Treatment of lung metastases in canine mammary cancer patientsL https://pubmed.ncbi.nlm.nih.gov/39273048/