Vaccine Against Canine Cancer Study (VACCS)

UW Veterinary Care’s Oncology Service at the School of Veterinary Medicine, is participating with two other veterinary schools in the largest clinical trial conducted to date for canine cancer. This study is funded by the Open Philanthropy Project through Arizona State University. Dr. David Vail is the Principal Investigator at UW for the Vaccine Against Canine Cancer Study (VACCS).

Cancer is the leading cause of death in dogs, accounting for approximately 30 percent of all deaths. Certain breeds have much higher likelihoods of cancer than others. Tumor antigens are proteins that can be recognized by the immune system as foreign and result in the attack of tumors by the immune system. Researchers have identified a series of new tumor antigens that appear to be produced in multiple types of cancer very early in tumor development, and are produced in cancers from many species (humans, dogs and mice). Vaccination of mice with these antigens can delay or prevent multiple types of cancer without side effects.

The goal of the VACCS trial is to determine whether vaccination with these novel tumor antigens is capable of reducing the likelihood of a dog developing cancer. Dogs between six and ten years of age will be eligible to be randomized to receive the vaccine or a placebo. The health of the dogs will be followed closely for up to five years and the rate of cancer development will be compared between the two treatment groups. In addition to potentially providing a new strategy for cancer prevention in dogs, if successful, this study could provide important justification for eventually looking at a similar approach in humans.

Molecular Targeted Radiotherapy

The research teams of Drs. Zachary Morris and Jamey Weichert at the UW Carbone Cancer Center have developed a new approach to the treatment of cancer that has spread to multiple places in the body (metastatic cancer). This approach involves stimulating the patient’s own immune system (immunotherapy) in combination with a low-dose of radiation therapy to recognize and destroy the cancer. It has been shown that low-dose radiation therapy, if delivered to all sites of cancer in a mouse, enables this combination immunotherapy approach to destroy tumor throughout the mouse; however, there are great difficulties in delivering conventional radiation therapy to all cancer sites in patients when cancer has spread to many sites. Instead, the teams are giving targeted radiation therapy that can be injected into a patient’s vein and can go throughout the body to preferentially deliver the radiation to tumors wherever they are located.

To direct the radiation therapy to all the tumor sites, the radioactive anticancer agent is linked to a molecule (called alkylphosphocholine) that when administered intravenously attaches preferentially to cancer cells and then the targeted radiation can kill the cancer cells. Through a study at UW Veterinary Care’s Oncology Service under Dr. David Vail’s direction, researchers are now ready to begin treating companion pet dogs with this new approach. This study is funded by the National Institutes of Health. What is learned from the treated dogs will help in the design of trials of this novel form of treatment in humans with metastatic cancer.

A New Approach to Activate Immune Rejection of Spontaneous Canine Melanoma

Melanoma is the most dangerous form of skin cancer and kills over 9,300 people a year in the United States. Melanoma is also the most common oral cancer in pet dogs and similar to humans, it is an aggressive cancer that spreads to lymph nodes, lungs, liver, brain, and kidney. Unfortunately, for both people and dogs, once melanoma spreads to distant sites it is usually incurable. However, new treatments that activate the patient’s own immune system (immunotherapy) to fight the melanoma have worked very well in some patients. The research group of Dr. Mark Albertini at the UW Carbone Cancer Center has been developing immunotherapy treatments predicted to work well in many or even most patients. Dr. Albertini was recently awarded a grant from the Veterans Administration to study an immunotherapy approach to the treatment of melanoma.

The goal of this study is to determine whether this new treatment approach is safe and has anti-melanoma activity in companion pet dogs that have been diagnosed with melanoma. The dogs in this study will be treated at UW Veterinary Care’s Oncology Service under the direction of Dr. David Vail. We are hoping that this treatment may let dogs with melanoma live longer or even be cured. Canine melanoma is very similar to human melanoma and it is expected that information from this study will guide further clinical trials in pet dogs and people diagnosed with melanoma.

Studies for the Treatment of Bone Cancer (Osteosarcoma)

Osteosarcoma (OSA) is a highly aggressive bone tumor that occurs in middle to older aged large and giant breed dogs and children in their first and second decades of life. It is estimated that OSA occurs with an incidence of 18,000 dogs per year and approximately 800 children per year in the United States. Despite the relatively low number of children afflicted with this disease, it is the second most common cancer in adolescents. In both species, treatment consists of combination chemotherapy and radical surgery. Despite aggressive treatment, metastatic disease is common and results in mortality rates in children of 30-40 percent within five years of diagnosis, making OSA the second highest cause of cancer-related death in children and adolescents. In dogs, mortality rates are higher with 85-90 percent of dogs succumbing to metastatic disease within two years. There are no effective treatments for metastatic disease and the current focus of drug development strategies is on prevention or treatment of metastases.

The UW School of Veterinary Medicine is currently participating in two clinical trials for the treatment of OSA in pet dogs. Dr. David Vail is directing these studies through the UW Veterinary Care Oncology Service. In both studies, dogs with OSA have undergone standard of care treatment for OSA. One study is aimed at preventing the development of metastatic disease and one is aimed at treating dogs that have developed spread of the OSA to their lungs.

Study 1: Evaluation of a Recombinant, Attenuated Listeria monocytogenes Expressing a Chimeric Human HER2/neu Protein in Dogs with OSA without Metastasis

The UW School of Veterinary Medicine is an active member of the Comparative Oncology Trials Consortium (COTC) which is a network of comparative oncology centers that is centrally managed by the NIH-NCI-Center for Cancer Research’s Comparative Oncology Program. This study is being conducted through the COTC.
The immune system plays an important role in identifying and targeting cancer cells in the body. In this study, we aim to use a new approach to stimulate the body’s own immune system to attack remaining tumor cells in dogs that have undergone limb amputation and chemotherapy for the treatment of OSA. We are using a vaccine made from the bacteria Listeria monocytogenes, which has been genetically modified to express a tumor protein (HER-2/neu) that is found in many cancer cells, including canine bone cancer cells and cancer stem cells. When injected into the bloodstream, the vaccine stimulates the immune system to attack cells expressing the HER-2/neu tumor protein. This approach aims to delay and/or prevent the spread of cancer (metastasis) following removal of the primary bone cancer tumor (limb amputation) and chemotherapy.
This study will evaluate the anticancer effect of this vaccine in dogs with OSA and compare it to currently ongoing studies of dogs with OSA being treated with amputation and chemotherapy, without the vaccine. In addition, what we learn from this study will be used to inform studies in people affected by OSA.

Study 2: Evaluation of a Novel Anticancer Drug in Combination with a Common Chemotherapy Drug for the Treatment of OSA Metastasis

Once OSA tumors are detected in the lungs, few effective treatment options are available and most chemotherapies are ineffective in treating these tumors. The patient’s quality-of-life is poor and their survival time tends to be short. Given this bleak outlook, there is clear need for helping these patients live better and longer lives. One reason why chemotherapy might not work well in dogs with OSA that has spread to the lungs is because the cancer cells have become resistant to normal tumor cell death-inducing signals produced by chemotherapy agents. Drugs which restore chemotherapy sensitivity of the tumor cells might have the potential to restore the effectiveness of traditional chemotherapy agents. Procaspace Activating Compound-1 (PAC-1) is a new drug that can sensitize tumor cells to the death-inducing signals produced by chemotherapy treatment. In recent studies, PAC-1 was well-tolerated by pet dogs with cancer. In this current clinical trial, PAC-1 treatment is being combined with the commonly used chemotherapy agent, doxorubicin, for the treatment of dogs with OSA that has spread to their lungs. PAC-1 is administered orally, once daily for seven days prior to each intravenous doxorubicin treatment for a total of four doxorubicin treatments. It is expected that this combination could shrink the OSA lung tumors and improve the overall quality-of-life and survival time of these dogs. This study is supported by a grant from the Puppy Up Foundation through the University of Illinois College of Veterinary Medicine.

A Novel Treatment for Dogs with T Cell Lymphoma
Lymphoma, the most common blood cancer of dogs, is an aggressive disease. There are basically two types of lymphoma affecting different blood cells: B-cell lymphoma and T-cell lymphoma. B-cell lymphoma is usually less aggressive than T-cell lymphoma. Approximately 30% of lymphomas are of the T-cell type and most correlate closely with a similar lymphoma in people called non-Hodgkin’s lymphoma, an aggressive cancer in people. While the majority of dogs with B- or T-cell lymphoma will initially respond to a course of chemotherapy using multiple drugs, the lymphoma will return in greater than 95 percent of dogs as the lymphoma becomes resistant to the chemotherapy. The average survival time for these dogs is approximately one year from diagnosis.

Recent evidence suggests that there exists a population of T-cell lymphoma cells that require a specific protein (called ITK) that contributes to the progression of the lymphoma. A novel, potent, and specific inhibitor of the effect of ITK (called CP-596) has shown anticancer activity against T-cell lymphoma. This drug is administered orally, twice daily. The objective of this study is to evaluate the safety and efficacy of CP-596 in pet dogs diagnosed with T-cell lymphoma. UW Veterinary Care’s Oncology Service, under the direction of Dr. David Vail, is participating in this multi-center trial which is funded by Corvus Pharmaceuticals. What is learned from this study will allow the design of expanded studies evaluating CP-596 for the treatment of T-cell lymphoma in both dogs and people.