02487: OX40 Checkpoint Molecule Targeted Antibodies for Cancer Immunotherapy in Dogs

One Health: Yes

Abstract

Checkpoint molecules play a key role in regulating T cell immunity against cancer (T cells are one type of immune cell called lymphocytes). Clinical trials of antibody therapeutics that target checkpoint molecules such as PD-1 in human oncology (e.g., Opdiva, Keytruda) have demonstrated remarkable results in inducing tumor regressions and cures, against a variety of different cancer types. This new era of cancer immunotherapy also has tremendous potential for treatment of cancer in dogs.  The investigators will begin development of a new, second-generation immunotherapy targeting the canine checkpoint molecule OX40 (CD134). Development of the first-generation PD-1 antibodies for canine oncology is already underway, and the investigator’s laboratory has been involved in evaluating immune responses to these antibodies. Studies in rodent models indicate that targeting the OX40 checkpoint molecule may be more effective than PD-1 for cancer immunotherapy. The investigators will use antibodies generated in their lab against the canine OX40 checkpoint molecule to investigate its role in regulating cancer immunity in dogs, as a first step in advancing OX40 antibodies to clinical trials in dogs with cancer. In this project, they will characterize canine OX40 antibodies, determine which immune cells express OX40 in dogs, determine how OX40 antibodies activate effector T cells in dogs, and how these antibodies trigger immune activation in tumor tissues to help accelerate development of OX40 checkpoint molecule targeted antibodies as next generation cancer immunotherapeutics for dogs.

Publication(s)

Dow, S. (2020). A Role for Dogs in Advancing Cancer Immunotherapy Research. Frontiers in Immunology, 10. https://doi.org/10.3389/fimmu.2019.02935