IGF::OT::IGF Topic 372 - SBIR Phase I: Development and Validation of Non- Mouse Reagents to Enable Preclinical Development of Novel Therapeutics - Moonshot

越来越多的人认识到，与传统的小鼠模型系统相比，患有自然发生的癌症的狗可能是评估癌症治疗的更好的模型系统。然而，利用狗来评估肿瘤免疫治疗的新兴类别受到合适试剂的可用性的限制，以指导犬免疫系统的反应。目前可用的大多数犬标记试剂是兔多克隆试剂，这些试剂不可再生，并且存在批次间的可变性。在这项I期研究中，我们建议使用我们专有的酵母抗体展示平台来生成针对3种犬标记物CD3e、pd - l1和IFN-gamma的兔单克隆抗体（mab），以证明我们的方法可以生成高亲和力、高特异性的兔单克隆抗体。与此同时，我们计划筛选现有的全人抗体库，以分离出一种功能阻断的抗犬PD-1抗体，该抗体也与人PD-1交叉读取，作为犬免疫治疗的原型，用于二期试验，使用该项目中产生的所有试剂来评估体内免疫反应。具有良好表征和可再生的犬类生物标志物试剂，将促进未来免疫治疗的发展。

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.