Discovery of public tumorspecific neoantigens (pTSNAs) and pTSNAreactive T cells arisen from hotspot mutations in canine hemangiosarcoma

Researchers will build on their discovery of “hotspot” mutations (tumor mutations shared between patients with the same cancer) to see if they can identify public tumor-specific neoantigens (pTSNAs) that are thought to play a role in immune response to cancer. Researchers hope findings will be a step toward a new immunotherapy that can be used in many different dogs suffering from hemangiosarcoma.

Co-sponsored with the Morris Animal Foundation, Grant Number: D24CA-536


Shaying Zhao, PhD, University of Georgia
Amount: $10,000

Reprogramming the Tumor Immune Niche in Canine Hemangiosarcoma

Hemangiosarcoma (HSA) is a common, devastating disease of dogs. The malignant tumor is seen frequently in older Golden Retrievers, German Shepherd Dogs, Portuguese Water Dogs, Labrador Retrievers, and Schnauzers, but it can occur in any dog of any breed at any age. Survival times of dogs with the tumor are short, even with surgical removal and standard of care treatment. Inflammation within the tumor tissue is common in canine HSA, and the immune response may contribute to tumor heterogeneity and prognosis for the dog. Yet, the immunological features in the context of the HSA niche are virtually unknown. The investigators have found that HSA cells have a strong capacity to promote proliferation and differentiation of hematopoietic stem and progenitor cells, with increased inflammatory cytokines, suggesting a niche regulatory function of HSA cells.

This study will focus on understanding the functional relationships between HSA cells and immune cells that contribute to the tumor niche to identify molecular mechanisms that regulate critical signaling pathways in canine HSA. This approach will improve our understanding of the tumor immunity and heterogeneity, as well as aid in patient selection for novel immunotherapies.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 2759


Jong Hyuk Kim, DVM, PhD; University of Minnesota
Amount: $5,000

Strategic Prevention of Canine Hemangiosarcoma: Lifetime Follow-Up (Shine-On)

The Shine On project is designed to utilize complementary technologies to reduce the impact of hemangiosarcoma in companion dogs. This novel, potentially disruptive approach is the first of its kind where artificial intelligence applied to the results of a blood test will be used to assign dogs to a risk category for the development of hemangiosarcoma. The test, called the Shine On Suspicion (SOS) Test is designed to detect hemangiosarcoma at its earliest stages of development before it becomes a clinically-detectable disease. Dogs that are considered to be at high risk based on the SOS Test results will be eligible to receive the drug eBAT for strategic prevention; that is, to eliminate emergent hemangiosarcoma tumors before they form. eBAT is a rationally designed drug developed in the laboratory to attack the cells that initiate and maintain the cancer, as well as to make the environment inhospitable for their growth.

For the initial phase of the Shine On project, investigators developed and refined the SOS Test and the artificial intelligence methods to assign dogs to specific diagnostic categories and started to establish the utility of the test in early detection in a group of 209 presumably healthy, pedigreed Golden Retrievers, Boxers, and Portuguese Water Dogs, 6 years of age or older.

In this continuation phase of the Shine On project, this group of dogs that had the SOS Test will be followed for their lifetimes to identify any diagnosis of cancer or another chronic disease, the cause of death, and date of death. In addition, a subset of dogs determined to be at high risk using the SOS Test will receive eBAT in the setting of prevention and also followed over their lifetime to establish their outcomes. This project expects to develop firm proof of concept to support larger clinical trials, and eventual deployment of this approach to the veterinary community setting for all dogs at risk of developing hemangiosarcoma.

Co-sponsored through the collaborative efforts and generosity of the Golden Retriever Foundation and American Boxer Charitable Foundation, Grant Number: 02806-MOU


Jaime Modiano, VMD, PhD ; University of Minnesota
Grant Period: 8/1/2020 – 7/31/2024
Amount: $269,238

Clinical Trial for Evaluation of Propranolol and Doxorubicin in the Treatment of Canine Hemangiosarcoma

Canine hemangiosarcoma is a largely incurable cancer in dogs, and treatment approaches to improve outcomes have remained relatively stagnant over the past few decades. Treatment remains a challenge partly because the cancer is frequently detected at an advanced stage and because these tumors are often resistant to chemotherapies. Recently published reports showed that propranolol, a drug used to treat heart disease in humans and dogs, substantially increased the survival time of human angiosarcoma patients when used in combination with standard of care treatments. Propranolol was also shown to sensitize hemangiosarcoma cells to doxorubicin, providing a more effective way to kill tumor cells. Because angiosarcoma is strikingly similar to canine hemangiosarcoma, this multi-institutional clinical trial has been designed to determine the efficacy of propranolol in dogs with hemangiosarcoma when used in combination with surgery and chemotherapy.

The main goal of the study is to establish whether propranolol in combination with doxorubicin following surgery improves outcomes for dogs when compared to the use of chemotherapy and surgery alone. The investigators will also evaluate the plasma concentrations of propranolol achieved during dosing to assess whether the levels of propranolol correlate to survival times. If successful, the findings from this approach will be rapidly conveyed to the veterinary community, and the guidelines provided to clinicians for the use of propranolol and doxorubicin for the treatment of canine hemangiosarcoma.

Co-investigators: David R. Brown, PhD, University of Minnesota; Michael O. Childress, DVM, MS, Purdue University; Jennifer Mahoney, DVM and Pascale Salah, DVM, University of Pennsylvania

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 02534


Erin Dickerson, PhD and Brian Husbands, DVM; University of Minnesota
Amount: $10,000

Prevalence of Bartonella spp. Infection in Dogs with Cardiac and Splenic Hemangiosarcomas within and between Geographic Locations

Splenic masses comprise ~50% of all canine splenic disease. Despite advances in imaging and pathologic definition, the etiology and medical relevance of splenic lesions in dogs are often ambiguous. While some splenic tumors are benign, approximately two-thirds are highly malignant and carry a poor prognosis. Hemangiosarcoma (HSA) accounts for the majority of canine malignant splenic tumors and occurs in many large dog breeds, including mixed breeds.A less common site of HSA localization is the heart (cardiac HSA). Risk factors for both cardiac and splenic HSA remain unclear, confounding development of preventative strategies.

The investigators recently reported a high prevalence of species of the bacterial genus Bartonella in dogs with HSA from North Carolina, suggesting a potential role in the initiation and/or progression of this cancer. Bartonella species exist worldwide and are transmitted by blood-sucking arthropods (e.g. ticks, fleas) and their presence in splenic tissue could potentially be explained by the fact that the spleen is primarily responsible for removal of blood-borne parasites from the systemic circulation.

The investigators will perform a comprehensive examination of the potential association between Bartonella infection and HSA by comparing the prevalence of Bartonella DNA in tumor and blood samples from both splenic and cardiac HSA cases, and also within and between distant geographical locations in the US. Ultimately, demonstration of a robust association between Bartonella infection and the development of HSA may lead to new opportunities for improved diagnosis, treatment and prevention of this devastating cancer.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 02519


Edward Breitschwerdt, DVM
North Carolina State University Office of Sponsored Programs
Amount: $10,000 in 2018, $10,000 in 2019

Disease Risks Associated with Spay and Neuter: A Breed-Specific, Gender Specific

This study extends the investigator’s recently completed AKC Canine Health Foundation-funded project studying 12 dog breeds to identify major differences in the degree to which spay or neuter may be related to an increase in joint disorders (hip dysplasia; cranial cruciate ligament tear) and/or cancers (lymphoma; hemangiosarcoma; and mast cell tumor).

The original breeds studied were: Labrador Retriever, Golden Retriever, German Shepherd Dog, Rottweiler, Boxer, Bulldog, Doberman Pinscher, Dachshund, Corgi (both breeds), Chihuahua, Yorkshire Terrier and Shih Tzu. Findings did not associate an increase in disease association in the small breeds with spaying or neutering, while in larger breeds disease risk was dependent upon gender, and whether the spay or neuter procedure was performed before or after one year of age (Hart, B.L., L.A. Hart, A.P. Thigpen and N. H. Willits. 2014. Long-term health effects of neutering dogs: Comparison of Labrador Retrievers and Golden Retrievers. PLoS ONE 9(7): 10.1371/journal.pone.0102241).

In this second phase, the following breeds have been added to the study: Great Dane, Australian Shepherd, Bernese Mountain Dog, Cocker Spaniel, Border Collie, Beagle, St. Bernard, Irish Wolfhound, Jack Russell Terrier, Pug, Maltese, Pomeranian, Miniature Schnauzer, Boston Terrier, Australian Cattle Dog, Shetland Sheepdog, English Springer Spaniel, Cavalier King Charles Spaniel, and West Highland White Terrier. Upon completion of the study, the major publisher, Wiley, has agreed to place the total data set of all 31 breeds on an open access website as a resource for breeders, dogs owners, researchers and veterinarians.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 02275


Dr. Benjamin L Hart, DVM, PhD
University of California, Davis
Amount: $3,000 in 2016 with an additional $2,000 in 2017

A Novel Approach for Prevention of Canine Hemangiosarcoma

Hemangiosarcoma, an aggressive form of cancer in dogs, is the cause of death for one out of every five Golden Retrievers in the United States. Portuguese Water Dogs and Boxers also have an especially high risk for this disease which is devastating for all dogs. Hemangiosarcoma is incurable partly because the cancer is detected at a very advanced stage when it is resistant to conventional therapies. Thus, an unconventional approach to improve outcomes for hemangiosarcoma patients will involve effective methods for early detection and for disease prevention.

This project will pair two novel technologies consisting of a patented test to detect hemangiosarcoma cells in blood samples, and a treatment that attacks the cells that establish and maintain the disease. Three milestones will be met: first, will be to expand understanding of the performance and utility of the blood test for cancer in dogs with active disease; second will be to confirm the utility of the test to predict disease progression in treated dogs; and third, will be to establish the performance of the test in the “early detection” setting (dogs at high risk without evidence of active cancer), and thus measure hemangiosarcoma prevention through eradication of the tumor initiating cells with the targeted, investigational drug.

This project will create tools to guide further development, licensing and deployment of these paired technologies against cancer, specifically hemangiosarcoma, with an ultimate goal for disease prevention in all dogs.

Co-sponsored through the collaborative efforts and generosity of the Golden Retriever Foundation and American Boxer Charitable Foundation. The AKC Canine Health Foundation supports the funding of this effort, and will oversee administration of funds and scientific progress reporting, Grant Number: 02234‐MOU

For details and logistics of this project, to include eligibility criteria and how to enroll, please visit Dr. Modiano’s page for the Shine On project.

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Canine Hemangiosarcoma – 2005 Research
Canine Hemangiosarcoma – The Road from Despair to Hope


Jaime F. Modiano, VMD, PhD
University of Minnesota
Amount: $432,000
Administrative Amount: $40,000

Health Implications of Early Spay/Neuter on Canine Health

Most dogs in the United States are spayed or neutered, and the default recommendation has been to perform these elective surgeries prior to physical maturity. However, recent data suggest that early spay and neuter may adversely impact the health and well-being of dogs.

In preliminary studies funded by CHF, Dr. Ben Hart of the UC Davis College of Veterinary Medicine found that early spay or neuter, prior to 12 months of age, was related to a significant increase in risk in five diseases of concern: hip dysplasia; cranial cruciate ligament tear; lymphosarcoma; hemangiosarcoma; and mast cell tumor.

CHF has now funded the second phase of Dr. Hart’s research in which he will expand his work to consider breed differences in vulnerability to joint disorders and risks of various cancers after early or late spay/neuter. Breeds considered will include: Labrador Retrievers, German Shepherd Dogs, and Dachshunds. Rottweilers, Chihuahuas, Standard Poodles, and Miniature Poodles will be included if resources and patient data are available. The expectation is that by inclusion of multiple breeds in phase II Dr. Hart will be able to develop a generalized understanding of the impact of early spay and neuter on disease risk in dogs. This in turn will enable veterinarians and breeders to make data-driven recommendations regarding timing of spay/neuter procedures to reduce the risk of development of multiple devastating diseases.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 1840

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Long-Term Health Effects of Neutering Dogs: Comparison of Labrador Retrievers with Golden Retrievers


Dr. Benjamin L Hart, DVM, PhD
University of California, Davis

Innovations in Prevention, Diagnosis, and Treatment of Cancer

Lymphoma and hemangiosarcoma are major health problems in Portuguese Water Dogs. This study collaborates with several top universities and researchers who are utilizing cutting edge technology to identify several regions of the genome that contain genetic, heritable, risk factors for lymphoma and hemangiosarcoma in Golden Retrievers. This information can then be applied to other breeds, including Portuguese Water Dogs. Tumor-specific mutations, when identified, can be clinically applied to reduce the incidence of these cancers, identify cancer earlier, and modify treatment plans to the individual patient.

Research Objective

Lymphoma and hemangiosarcoma are major health problems in Golden Retrievers, causing both suffering and premature death. Through ongoing collaboration, Drs. Jaime Modiano, Matthew Breen, and Kerstin Lindblad-Toh have identified several regions of the genome that contain genetic heritable risk factors for lymphoma and hemangiosarcoma in Golden Retrievers. They have tumor-specific mutations that occur recurrently in both cancers, some of which are linked to duration of remission when treated with standard of care. Their results indicate that a few heritable genetic risk factors account for as much as 50% of the risk for these cancers.

These findings offer the potential to develop tests and strategies for DNA tests that can predict risk for individual dogs, as well as to manage risk across the population as a whole. Indeed, both the inherited risk factors and tumor mutations point to pathways that have been implicated in the pathogenesis of lymphoma and hemangiosarcoma, and thus should inform the development of targeted therapies. In the current study, Drs. Modiano, Breen, and Lindblad-Toh will find the precise mutations for the heritable genetic risk factors and to validate markers (mutations) used to determine risk at the heritable loci in a larger independent population of Golden Retrievers from the United States and from Europe in order to develop robust risk prediction tools and an accompanying DNA test. Further, they will identify and characterize tumor mutations and study their relationship to the heritable risk factors, tumor pathogenetic mechanisms, and disease outcome.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 1889-G

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Dr. Jaime F Modiano, VMD PhD
University of Minnesota

Matthew Breen, PhD, CBiol, FSB
North Carolina State University

Testing Strategies to Treat Drug-Resistant Hemangiosarcomas

Lysosomal Drug Sequestration by CSF-1R (High) Tumor Cells Contributes to Drug Resistance in Canine Hemangiosarcoma

Summary: Investigators are assessing the potential for a specific tumor-cell population in canine hemangiosarcoma to sequester drugs within their lysosomes as a novel mechanism of drug resistance.

Description: Canine hemangiosarcoma is a common and highly metastatic cancer that affects all breeds of dogs. These tumors are particularly drug resistant, which makes them difficult to treat.

The investigators recently identified a more drug-resistant cell population in hemangiosarcoma. These cells appear to be extremely efficient in isolating cancer drugs and preventing them from reaching their targets. The investigators will use several strategies to try to disrupt this process and they will determine whether any of these approaches improves drug responses and diminishes drug resistance. This could lead to more effective treatment of this difficult cancer.

Co-sponsored with the Morris Animal Foundation, Grant Number: D14CA-047


Dr. Erin B. Dickerson
University of Minnesota