Simple SummaryImmunotherapy for the treatment of cancer seeks to use the body’s own immune system to recognize and eliminate tumor cells. Some of the most successful immunotherapies in human medicine have relied on the generation of biological reagents specific to humans, such as tumor antigen vaccines and humanized monoclonal antibodies. Veterinarians would like to incorporate immunotherapies into oncogenic medicine; however, the readily available reagents are biological therapies designed for human use, and their utility in veterinary medicine remains unknown. In some instances, such as tumor antigen vaccination, humanized reagents may prove advantageous in animal species. In other instances, such as the use of humanized monoclonal antibodies, the treatment may fail as a result of the animal’s own immune system rejecting the human reagent. Here, we review the potential use of these reagents for veterinary oncology and explore other possible reagents that may have “universal” applicability in different animal species.AbstractThe emergence of immunotherapy for the treatment of human cancers has heralded a new era in oncology, one that is making its way into the veterinary clinic. As the immune system of many animal species commonly seen by veterinarians is similar to humans, there is great hope for the translation of human therapies into veterinary oncology. The simplest approach for veterinarians would be to adopt existing reagents that have been developed for human medicine, due to the potential of reduced cost and the time it takes to develop a new drug. However, this strategy may not always prove to be effective and safe with regard to certain drug platforms. Here, we review current therapeutic strategies that could exploit human reagents in veterinary medicine and also those therapies which may prove detrimental when human-specific biological molecules are used in veterinary oncology. In keeping with a One Health framework, we also discuss the potential use of single-domain antibodies (sdAbs) derived from camelid species (also known as Nanobodies™) for therapies targeting multiple veterinary animal patients without the need for species-specific reformulation. Such reagents would not only benefit the health of our veterinary species but could also guide human medicine by studying the effects of outbred animals that develop spontaneous tumors, a more relevant model of human diseases compared to traditional laboratory rodent models.