IGF::OT::IGF Topic 372: Development and Validation of Canine scFvs for Pre-Clinical Development of Targeted Therapeutics - Moonshot

这项SBIR的目标是为Ventigenics的犬源ScFv噬菌体展示平台提供概念验证，以快速、经济高效地生产高度通用的犬源ScFv。针对CD19、CD3和CTLA4的单链抗体将被分离出来，这三种高价值的免疫分子是人类癌症免疫治疗中基于抗体的策略的靶点。选定的单链抗体将被测序，并确定结合亲和力。通过宾夕法尼亚大学兽医学院的合作者，Ventigenics可以获得犬类细胞、细胞系和组织，提供无与伦比的能力来验证分离的单链抗体。分离的单链抗体的靶向性和功能将使用标准的免疫学分析进行验证。为了证明scFv形式的多功能性和广泛的适用性，我们将选择一种针对CD19的先导犬单链抗体，并用它来产生1)犬CAR T细胞和2)单抗。CD19特异性单链抗体的特异性、功能性和体外诊断将得到验证，包括流式细胞术和免疫组织化学。这项工作的成功完成将为患癌症的狗提供有效的体内使用试剂，使在临床相关的大型动物癌症模型中探索组合方法和相关生物标记物的反应成为可能。此外，这项工作将为兽医市场提供平行的有前景的免疫疗法。

The goal of this SBIR is to provide proof-of-concept of Vetigenics’ canine-derived scFv phage display platform for rapid, cost effective production of highly versatile, canine-derived scFvs. scFvs against CD19, CD3 and CTLA4, three high-value, immunological molecules being targeted by antibody-based strategies in human cancer immunotherapy, will be isolated. Selected scFvs will be sequenced and binding affinities determined. Through its collaborators at the University of Pennsylvania School of Veterinary Medicine, Vetigenics has access to canine cells, cell lines and tissues providing an unparalleled ability to validate isolated scFv. Target specificity and functionality of isolated scFvs will be validated using standard immunological assays. To demonstrate the versatility and broad applicability of the scFv format, a lead canine CD19-specific scFv will be selected and used to generate 1) canine CAR T cells and 2) monoclonal antibodies. CD19-specific scFv formats will be validated for specificity, functionality and in vitro diagnostics including flow cytometry and immunohistochemistry. Successful completion of this work will provide validated reagents for in vivo use in dogs with cancer, enabling exploration of combination approaches and correlative biomarkers of response in a clinically relevant large animal cancer model. In addition, this work will provide parallel promising immunotherapeutics for the veterinary market.