Bone Cancer Immunotherapy Using a Genetically Modified Salmonella
By Vicki Wilke, D.V.M., Ph.D., Diplomate ACVS1,2, and Emily Lipsitz, M.D. (Board Certified in Pediatric Hematology Oncology)3
1Department of Veterinary Clinical Science, College of Veterinary Medicine; 2Masonic Cancer Center; 3Department of Pediatrics, School of Medicine
Salmonella is an organism that strikes fear due to its potential to cause severe gastrointestinal illness, but it is not a word many people associate with cancer therapy. Think again. Dr. Dan Saltzman of the University of Minnesota Medical School and his colleagues have taken Salmonella organisms, weakened them using genetic engineering to eliminate their disease-causing potential, and developed a new drug by adding Interleukin-2 (IL-2), a series of proteins that act as “flavors” to activate the immune system.
Salmonella organisms like to grow in environments such as those created by tumors, and they seem to have special affinity for bone cancer. The development of Salmonella-IL2 has also led to a special collaboration between the University of Minnesota Medical School and the College of Veterinary Medicine to utilize it in our canine patients.
Osteosarcoma (OSA) is the most common bone tumor in dogs. In approximately 90 percent of dogs with OSA, the cancer has already spread by the time they are diagnosed. With surgery alone, dogs have a median survival of three to four months. With chemotherapy, the median survival can increase to about nine to fourteen months.
To improve survival in patients with OSA, we must develop more effective treatments. One treatment type that has shown promise is immunotherapy – the use of the immune system to kill metastatic tumor cells. IL2 is a pro-inflammatory protein made by the immune system that aids in cell death, forming the basis for its use in cancer immunotherapy. In a new study underway at the College of Veterinary Medicine, we will evaluate safety and efficacy of a genetically modified Salmonella carrying the IL2 gene (Salmonella-IL2) in the treatment of dogs with spontaneous bone cancer. Salmonella-IL2 has been shown to be safe and to reduce tumor volume (size) in various animal species. There is an ongoing early clinical trial in human patients with no toxicities noted thus far. If successful, this treatment will be further developed to improve the outcome of dogs with osteosarcoma.
Dogs need to meet certain criteria to qualify for the study. Dogs that have untreated osteosarcoma that has not spread beyond the primary site and are otherwise in good health may be eligible.
Dogs cannot have received coticosteroids (prednisone,dexamethasone) for two weeks prior to entering the study, and dogs that have already been treated with surgery, chemotherapy, or radiation therapy are not eligible. Similarly, dogs that have consumed raw foods or have a positive fecal culture for Salmonella are not eligible for this study.
Eligible dogs will undergo a specialized form of imaging called positron emission tomography/ computed tomography (PET/CT). On day one patients will undergo a bone biopsy and receive their first oral dose of Salmonella IL2. Recheck evaluations and diagnostic blood work, urine tests, and fecal culture will be performed on days three and seven. Amputation will be performed on day 10. Dogs will then have a recheck evaluation and second dose of Salmonella IL2 on day 21, when chemotherapy with doxorubicin will be initiated. A final recheck and diagnostic blood work will occur on day 28, which is the official end of the study. However, dogs will continue to receive doxorubicin and Salmonella IL2 therapy every three weeks for five total treatments. A recheck PET/CT will be performed at six months to assess efficacy.
There is a financial incentive for participation. Specifically, the study will cover the costs of the study visits on day one (PET/CT, bone biopsy, and Salmonella IL2 therapy), rechecks, and the costs associated with amputation, up to a total of $2,000. All costs associated with PET/CT imaging will also be covered by the study.
An opening date for this trial is pending. Check the CVM Clinical Investigation Center website at www.cvm.umn.edu/cic/ for more information, applications to enroll dogs in clinical trials, or to make a contribution to support this research.
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Participate in canine health research by providing samples or by enrolling in a clinical trial. Samples are needed from healthy dogs and dogs affected by specific diseases.