Development and validation of anti-canine reagents to enable pre-clinical development of novel therapeutics

与传统的小鼠模型系统相比，带有自然发生癌症的狗可以作为评估新的癌症免疫疗法的更好的模型系统，并且还可以提供目标患者组。然而，目前犬癌患者的使用受到可用于监测犬类免疫反应的合适试剂的限制。目前市售的犬类生物标记物试剂大多为兔多克隆试剂，这些试剂不可再生，且存在批次-批次可变性。继他们在第一阶段取得成功后，该公司计划在这里使用他们新型的酵母兔抗体展示平台来发现针对26个犬类生物标志物的扩展小组的高亲和力、高特异性的兔单抗。同时，AvantGen计划优化在第一阶段分离的犬化抗犬PD-1抗体作为犬只免疫疗法，然后在患有淋巴瘤的宠物狗身上进行一项试点研究，以评估其安全性和有效性，作为与标准护理化疗同步治疗的方法，使用该项目期间产生的生物标记物试剂来评估治疗的体内免疫反应。成功的结果将导致一组高质量的、特征良好的、可再生的犬类生物标志物试剂，这将促进未来免疫疗法的发展，并为犬淋巴瘤提供一种新的治疗方法。

Dogs with naturally occurring cancers can serve as a better model system for evaluating novel cancer immuno-therapeutics than the traditional mouse model systems, and also provide a target patient group. However, use of canine cancer patients is currently limited by the availability of suitable reagents to monitor canine immune responses. The majority of commercially-available reagents for canine biomarkers are rabbit polyclonal reagents, which are not renewable and suffer from lot-lo-lot variability. Following their success in Phase I, here the company proposes to use their novel yeast rabbit antibody display platform to discover high affinity, highly specific rabbit monoclonal antibodies against an expanded panel of 26 canine biomarkers. In parallel, AvantGen plans to optimize the caninized anti-canine-PD-1 antibody isolated in Phase I as a canine immunotherapeutic, then perform a pilot study in pet dogs with lymphoma to assess its safety and efficacy as concurrent therapy with standard of care chemotherapy using the biomarker reagents generated during this project to assess in vivo immune responses to treatment. A successful outcome will result in a panel of high quality, well characterized, renewable reagents for canine biomarkers that will facilitate future development of immunotherapeutics plus provide a novel treatment for canine lymphoma.