Role of companion dogs in cancer immunotherapy development

Abstract

Rodent models for evaluating new cancer immunotherapies often fail to fully recapitulate the complexity of immune interactions that occur in cancer patients. Companion dogs with spontaneously developing cancers more closely resemble humans immunologically than rodents. This resemblance results in part because their immune systems have been educated early by repeated vaccinations and viral and bacterial infections, with further sculpting later in life by tumors that typically take months to develop. Moreover, dogs possess all of the major leukocyte subsets present in humans, both in circulation and within tumor tissues. The major canine cancer models most relevant to evaluating new cancer immunotherapies include osteosarcoma, glioma, non-Hodgkin lymphoma, melanoma, uroepithelial cancer, and head and neck cancers. Each of these cancers recapitulates to varying degrees the genetics, histology, and biological behaviors of the human analogous cancers. Immune therapies under active investigation in companion dogs include chimeric antigen receptor T-cell therapies, myeloid cell-targeted therapies, radioimmunotherapy, and tumor vaccines. Results of these ongoing studies are expected to accelerate the translation to humans of promising therapy combinations, while also identifying approaches that are ineffective or associated with unacceptable immunological toxicities.