2629: Clinical and Immunological Outcomes in Dogs with Osteosarcoma Treated with Intratumoral Interleukin-12 Microspheres

Grant Status: Closed

Grant Amount: $43,800.03
Dr. Stuart Helfand, DVM, University of Wisconsin, Madison
January 1, 2004 - December 31, 2005
Sponsor(s): Akita Club of America, Inc., American Bloodhound Club, American Boxer Charitable Foundation, American Bullmastiff Association, American German Shepherd Dog Charitable Foundation, Inc., Borzoi Club of America, Flat-Coated Retriever Foundation, Golden Retriever Foundation, Great Pyrenees Club of Puget Sound, Irish Wolfhound Club of America, Inc., Irish Wolfhound Foundation, Jeffrey Pepper, Newfoundland Club of America Charitable Trust, Rottweiler Health Foundation, St. Bernard Club of America, Starlight Fund
Breed(s): -All Dogs
Research Program Area: Treatment

Abstract

Appendicular osteosarcoma, or bone cancer of the limbs, is an important tumor in dogs representing nearly 10 percent of all canine cancers. Despite progress in treating canine osteosarcoma using a combination of limb amputation and chemotherapy, life expectancy is not usually extended by more than 6-10 months compared to amputation alone. Death is due to dissemination of cancer cells beyond the leg and it is estimated that the cancer has already spread in at least 95 percent of dogs when it is initially diagnosed. Novel treatment regimens are urgently needed to improve the lives of large breed dogs such as Golden, Labrador and other Retrievers, Rottweilers, Irish Wolfhounds, Great Danes, German Shepherds and others that are at greatest risk for developing this cancer. Stimulating the immune system of dogs with cancer has been a goal of veterinary cancer researchers for more than 20 years and osteosarcoma is a tumor that has shown positive responses to some of these interventions. This research proposes to add a potent new form of immunostimulation to the standard treatment for canine osteosarcoma. This strategy uses a powerful stimulant of the immune system called interleukin-12 (IL-12) that has been shown to induce strong antitumor responses in experimental animal models. Stimulated by IL-12, immune cells tolerant of cancer can be triggered to specifically kill cancer cells throughout the body. What�s more, the cells have long-term memory for the specific cancer. Our laboratory has shown that IL-12 enhances killing of osteosarcoma cells by immune cells from dogs. We propose that injection of IL-12 directly into limb osteosarcoma using a novel (microsphere) formulation resulting in slow IL-12 release within the tumor environment will promote active antitumor immunity in dogs with osteosarcoma and lengthen their survival time. A number of pertinent immunological questions will also be addressed.

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