PFI-TT: Increased affinity of cancer therapeutic via single-domain antibody and dimer targeting of canine PD-1

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The broader impact/commercial potential of this Partnerships for Innovation - Technology Translation (PFI-TT) project includes the development of safe, effective, and affordable treatments for animal diseases including cancer in dogs. A robust immune system is critical for effective treatment of cancer. Beyond surgery, radiation, and chemotherapeutics, new approaches include agents shown to block tumors from circumventing the body’s immune defenses. The societal outcomes of this work may include prototype and manufacturing optimization to produce biological molecules that bolster immune activity at comparatively low cost. Like the very expensive, though effective, human therapeutic counterparts, alternative platforms can be substituted at reduced cost, making the treatment accessible to animals, improving their lives and their caretakers’ lives. Greater demands have been placed on healthcare for new flexible technologies to treat disease in a rapid and inexpensive manner. A commercial opportunity resides in providing pet owners and veterinarians an effective, economical, and safe treatment for the nearly 6 million dogs diagnosed yearly with cancer. Creation of manufacturing processes of these new prototypic therapeutics will be utilized to demonstrate the feasibility of project outcomes and contribute to the general public's appreciation of this platform in generating less expensive biologics-based therapies. The proposed project seeks to produce a prototype therapeutic for the treatment of cancer in dogs. As cancer is a leading cause of death in people and dogs, new technologies need to be brought forth. Development of cutting-edge therapeutics for humans and animals requires relevant and robust model systems that provide predictable outcomes. Antibodies, a proven therapeutic platform, are large, complex proteins, that are expensive to develop and manufacture. Different configurations of several proprietary subunit single domain antibodies which are smaller proteins, cheaper to develop and produce will be examined. An optimal dual epitope-binding prototype, specific to an orthologous canine target, will be constructed using recombinant DNA methods and produced in Yeast expression systems. Binding affinity will be measured by bio-layer interferometry. Feasibility testing and optimization of large-scale production will be examined, and purity and functional activity assessed. The anticipated results are that one or more of these combinations will produce a robust binding protype and thus targeting the orthologous canine molecule could provide a potent therapeutic benefit in treatment of canine cancers.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.