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

人们越来越认识到，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用于评估癌症治疗的更好的模型系统。然而，使用犬评价肿瘤学免疫治疗的新兴类别受到指导犬免疫系统反应的合适试剂的可用性的限制。目前可获得的用于犬标记物的大多数试剂是兔多克隆试剂，其不可再生并且存在批次间变异性。在该I期研究中，我们建议使用我们的专有酵母抗体展示平台来产生针对3种犬标志物（CD 3e、PD-L 1和IFN-γ）的兔单克隆抗体（mAb），以证明我们的方法产生高亲和力、高特异性兔mAb的能力。同时，我们计划筛选我们现有的全人抗体文库，以分离功能阻断抗犬PD-1抗体，该抗体也与人PD-1交叉读取，作为原型犬免疫素用于II期，以使用本项目期间产生的所有试剂评估体内免疫应答。成功的结果将产生高质量的一组，用于犬生物标志物的良好表征和可再生的试剂将促进免疫治疗剂的未来发展。

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.