Development of OX40 agonists for canine cancer immunotherapy
Damien Ruiz,
Chloe Haynes,
Jonathan Marable,
Chetan Pundkar,
Rebecca L. Nance,
Deepa Bedi,
Payal Agarwal,
Amol S. Suryawanshi,
Amarjit Mishra,
Bruce F. Smith,
Maninder Sandey
Affiliations
Damien Ruiz
Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA
Chloe Haynes
Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA
Jonathan Marable
Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA
Chetan Pundkar
Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA
Rebecca L. Nance
Scott Ritchy Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL, USA
Deepa Bedi
Biomedical Sciences, Tuskegee University, Tuskegee, AL, USA
Payal Agarwal
Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA; Scott Ritchy Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL, USA
Amol S. Suryawanshi
Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA
Amarjit Mishra
Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA
Bruce F. Smith
Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA; Scott Ritchy Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL, USA
Maninder Sandey
Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA; Corresponding author
Summary: Recent breakthroughs in cancer immunotherapy have provided unprecedented clinical benefits to human cancer patients. Cancer is also one of the most common causes of death in pet dogs. Thus, canine-specific immune therapies targeting similar signaling pathways can provide better treatment options for canine cancer patients. Here, we describe the development and characterization of two canine-specific anti-OX40 agonists to activate OX40 signaling. We show that canine OX40, like human OX40, is not expressed on resting T cells, and its expression is markedly increased on canine CD4 T cells and Tregs after stimulation with concanavalin A (Con-A). cOX40 is also expressed on tumor-infiltrating lymphocytes (TILs) in canine osteosarcoma patients. The canine-specific OX40 agonists strongly activates cPBMCs by increasing IFN-γ expression and do not require Fc receptor-mediated cross-linking for OX40 agonism. Together, these results suggest that cFcOX40L proteins are potent OX40 agonists and have the potential to enhance antitumor immunity in canine cancer patients.
