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

IGF::OT::IGF 主题 372：用于靶向治疗临床前开发的犬 scFv 的开发和验证 - Moonshot

• 批准号: 9915565
• 负责人: Brendan Pucell
• 金额: $ 5.5万
• 依托单位: VETIGENICS LLC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-17 至 2019-07-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9915565
• 关键词: Affinity; Animal Cancer Model; Antibodies; Binding; CD19 gene; CD3 Antigens; CTLA4 gene; Canis familiaris; Cell Line; Cells; Development; Diagnostic; Flow Cytometry; Goals; Human; Immune Targeting; Immunohistochemistry; Immunologics; Immunology procedure; Immunotherapeutic agent; In Vitro; Lead; Libraries; Lymphoma; Malignant Neoplasms; Monoclonal Antibodies; Pennsylvania; Phage Display; Production; Reagent; Small Business Innovation Research Grant; Specificity; Therapeutic Uses; Tissues; Universities; Validation; Veterinary Medicine; Veterinary Schools; Work; base; cancer immunotherapy; chimeric antigen receptor T cells; clinically relevant; cost effective; in vivo; preclinical development; response biomarker; targeted treatment

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.

该SBIR的目标是提供Vetigenics的犬源性scFv噬菌体展示平台的概念验证，用于快速，成本有效地生产高度通用的犬源性scFv。将分离针对CD19、CD3和CTLA4的scFv，这三种高价值的免疫分子在人类癌症免疫治疗中被基于抗体的策略靶向。将对选择的scFv进行测序并确定结合亲和力。通过其在宾夕法尼亚大学兽医学院的合作者，Vetigenics可以获得犬细胞，细胞系和组织，提供无与伦比的能力来验证分离的scFv。分离的scFv的靶特异性和功能性将使用标准免疫学测定来验证。为了证明scFv形式的通用性和广泛适用性，将选择前导犬CD19特异性scFv并用于产生1）犬CAR T细胞和2）单克隆抗体。将验证CD19特异性scFv形式的特异性、功能性和体外诊断，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有癌症的狗的体内使用提供经验证的试剂，从而能够在临床相关的大型动物癌症模型中探索组合方法和反应的相关生物标志物。此外，这项工作将为兽医市场提供平行的有前途的免疫治疗药物。