Abstract 1693: Multi-national, multi-center collaboration to develop a novel gene expression tool for comparative translational immuno-oncology
Authors: Nicola Mason, Christina Bailey, Erin Piazza, Alexander F. Haake, Achim D. Gruber, Cheryl London, M. R. Chambers, Steven W. Dow, G. Elizabeth Pluhar, Alina K. Langenhagen, Dhawan Deepika, Deborah W. Knapp, Qi Long, Robert B. Rebhun
Journal: Cancer Research (2021)

Abstract Harnessing the immune system to eliminate cancer and prevent its recurrence is proving to be a powerful therapeutic approach that has achieved unprecedented successes in hematological malignancies and some malignancies with a high tumor burden. Next generation immune therapies to improve clinical responses and widen the reach of immunotherapy are being designed at a rapid pace, and informative pre-clinical testing of these approaches can be greatly facilitated using immune competent animals with spontaneous tumors. Pet dogs are immunologically outbred, immune competent and develop spontaneous tumors such as non-Hodgkin's lymphoma, glioblastoma, osteosarcoma, urothelial carcinoma and melanoma that share remarkable clinical, biological and genetic features with their human counterparts. As such, pre-clinical testing of immune therapeutic approaches in dogs with cancer promises to accurately inform human clinical trial design. For this comparative approach to provide maximum information to accelerate human clinical translation of next generation immunotherapies and identify correlative biomarkers of therapeutic response, it is necessary to develop research tools for deep interrogation of the canine immune response. Here we present work conducted through a year-long, multi-center, global collaboration resulting in the creation of a novel gene expression tool for studies of the immune response in dogs treated with immuno-oncology and targeted therapies. This original approach utilizes the NanoString's nCounter® platform and is termed the Canine IO Panel, with inclusion of 800 canine genes for studying the immune response. The panel can be used with tissue, blood or other biospecimens and represents a companion panel to the widely recognized nCounter Human IO 360™ panel currently in use with human clinical trials. The customizable panel segments genes into 8 core components including Cytokine &amp; Chemokine Signaling, Interferon Signaling, Checkpoint Signaling, Complement Cascade, Immune Cell Abundance, Tumor Immunogenicity, Inhibitory Tumor Mechanisms, and Stromal Factors. Genes were selected based on their relevance for the study of oncology as well as expression profiles from both RNA-Seq and nCounter experiments. Additionally, the canine reference transcriptome, based on CanFam3.1 was utilized for designing the probes; the known genomic variability of dogs in addition to the nCounter hybridization chemistry result in compatibility across a variety of breeds. This new Canine IO panel, used in conjunction with the nCounter platform and correlated with the abundance of data that exist on the platform for similar human IO studies, creates a powerful tool for researchers undertaking comparative human and veterinary studies aiming to develop and improve the understanding and treatment of both canine and human cancers. Citation Format: Nicola Mason, Christina Bailey, Erin Piazza, Alexander F. Haake, Achim D. Gruber, Cheryl London, M. R. Chambers, Steven W. Dow, G. Elizabeth Pluhar, Alina K. Langenhagen, Dhawan Deepika, Deborah W. Knapp, Qi Long, Robert B. Rebhun. Multi-national, multi-center collaboration to develop a novel gene expression tool for comparative translational immuno-oncology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1693.