Abstract: Embodiments of the present invention relate to compositions and methods for activating canine OX40 to treat a condition in dogs. In certain embodiments, the condition can be cancer or an immunosuppressed condition in dogs and OX40 activation treats, ameliorates or prevents onset or progression of the condition. In other embodiments, compositions disclosed herein generally relate to compositions including, but not limited to, activating antibodies having specific affinity for OX40 for inducing activity of canine OX40. In other embodiments, compositions disclosed herein can be used for treating certain cancers or an immunosuppressed condition to treat the cancer or alleviate immunosuppression in dogs. In certain embodiments, other immune activators can be administered in combination with OX40 activating antibodies such as Toll-Like Receptor (TLR) ligands alone or in combination with other non-specific immunostimulant agents.