422: Tailored Antitumor Vaccines for Canine Hemangiosarcoma

Grant Status: Closed

Grant Amount: $114,530
Don Bellgrau, PhD; University of Colorado Cancer Center
July 1, 2005 - June 30, 2007

Sponsor(s): Alaskan Malamute Research Foundation, Inc., English Setter Association of America, Inc., Golden Retriever Foundation, Keeshond Club of America, Orthopedic Foundation for Animals, Samoyed Club of America Education & Research Foundation, Siberian Husky Club of America Trust

Breed(s): -All Dogs
Research Program Area: Oncology - Hemangiosarcoma
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Abstract

Canine hemangiosarcoma (HSA) is an incurable tumor of cells that line blood vessels. Of the approximately 65 million owned dogs in the United States, between 1.5 and 2.5 million will get this disease and die from it. We are developing tests to detect this tumor in its early stages when the immune system may be directed to eliminate it. Immune system cells must see proper "targets" (antigens) for an effective attack. We have identified such antigens that can be incorporated into effective anti-tumor vaccines. Preliminary experiments in laboratory mice show that about 90 percent of animals that receive no vaccine develop tumors, but 100 percent of mice that receive the specific tumor vaccine are protected from tumor growth. We predict that incorporation of these specific antigens into dog specific HAS vaccines will prevent tumor growth. These "tailored" vaccines that are specific for each patient�s tumor can be generated in days, and therefore, this approach is practical for clinical applications. We will validate clinical responses and immunologic outcomes in a mouse model, with long-term goals of developing treatment protocols to improve the quality of life and survival of dogs with HSA.

Publication(s)

Kim, J.-H., Frantz, A. M., Sarver, A. L., Gorden Klukas, B. H., Lewellen, M., O’Brien, T. D., … Modiano, J. F. (2018). Modulation of fatty acid metabolism and immune suppression are features of in vitro tumour sphere formation in ontogenetically distinct dog cancers. Veterinary and Comparative Oncology, 16(1), E176–E184. https://doi.org/10.1111/vco.12368
 
Kim, Jong-Hyuk, Frantz, A. M., Anderson, K. L., Graef, A. J., Scott, M. C., Robinson, S., … Modiano, J. F. (2014). Interleukin-8 promotes canine hemangiosarcoma growth by regulating the tumor microenvironment. Experimental Cell Research, 323(1), 155–164. https://doi.org/10.1016/j.yexcr.2014.02.020
 
Tamburini, B. A., Phang, T. L., Fosmire, S. P., Scott, M. C., Trapp, S. C., Duckett, M. M., … Modiano, J. F. (2010). Gene expression profiling identifies inflammation and angiogenesis as distinguishing features of canine hemangiosarcoma. BMC Cancer, 10(1). https://doi.org/10.1186/1471-2407-10-619
 
Tamburini, B. A., Trapp, S., Phang, T. L., Schappa, J. T., Hunter, L. E., & Modiano, J. F. (2009). Gene Expression Profiles of Sporadic Canine Hemangiosarcoma Are Uniquely Associated with Breed. PLoS ONE, 4(5), e5549. https://doi.org/10.1371/journal.pone.0005549
 
Tonomura, N., Elvers, I., Thomas, R., Megquier, K., Turner-Maier, J., Howald, C., … Lindblad-Toh, K. (2015). Genome-wide Association Study Identifies Shared Risk Loci Common to Two Malignancies in Golden Retrievers. PLOS Genetics, 11(2), e1004922. https://doi.org/10.1371/journal.pgen.1004922
 
Megquier, K., Turner-Maier, J., Swofford, R., Kim, J.-H., Sarver, A. L., Wang, C., … Lindblad-Toh, K. (2019). Comparative Genomics Reveals Shared Mutational Landscape in Canine Hemangiosarcoma and Human Angiosarcoma. Molecular Cancer Research, 17(12), 2410–2421 https://doi.org/10.1158/1541-7786.MCR-19-0221

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