Topic 372: Development and Validation of Non- Mouse Reagents to Enable Preclinical Development of Novel Therapeutics

There is an increasing appreciation that dogs with naturally occurring cancers may be a better model system for evaluating cancer therapeutics than the traditional mouse model systems. However, use of dogs for evaluating the emerging class of immunotherapeutics for oncology is limited by the availability of suitable reagents to mentor the response of the canine immune system. The majority of reagents for canine markers that are currently available are rabbit polyclonal reagents, which are not renewable and suffer from lot-to-lot variability. In this Phase I study we propose to use our proprietary yeast antibody display platform to generate rabbit monoclonal antibodies (mAbs) against 3 canine markers, CD3e, PD-L 1 and IFN-gamma to demonstrate the power of our approach to generate high affinity, highly specific rabbit mAbs. In parallel we plan to screen our existing fully-human antibody libraries to isolate a function-blocking anti-canine PD-1 Antibody that also cross-reads with human PD-1 as a prototypic canine immunotherapeutic to be used in Phase II to assess in vivo immune responses using all the reagents generated during this project A successful outcome will result in a panel of high quality, well characterized and renewable reagents for canine biomarkers that will facilitate future development of immunotherapeutics.