PO.ET02.05 · 实验与分子治疗

发光测定平台加速兽医免疫肿瘤学中的治疗性抗体开发

Luminescent assay platforms accelerate therapeutic antibody development in veterinary immuno-oncology

海报缩略图:发光测定平台加速兽医免疫肿瘤学中的治疗性抗体开发
编号 1656 展板 15 时间 4/20 09:00–12:00 区域 Section 11 主讲 Jun Wang, MS
分会场 Antibody Technologies and Platforms 1
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作者与单位 Authors & Affiliations

Jun Wang, Denise Garvin, Ildiko Kasza, Jim Hartnett, Mei Cong, Jamison Grailer

Promega, Madison, WI

摘要 Abstract

中文摘要
免疫肿瘤学的进展日益依赖转化动物模型来阐明作用机制(MoA)、药代动力学和治疗潜力。除了在人类治疗中的临床前应用价值外,这些模型对于开发兽医肿瘤学中的新型生物制剂也至关重要,尤其是在犬类癌症中,这些癌症与人类疾病在关键的人口统计学、免疫学和分子特征上具有共性。这一研究领域的一个主要局限是缺乏稳健的分析工具来表征物种特异性的抗体功能和受体结合。我们开发了一套发光、基于细胞的生物测定,用于定量Fc介导的效应机制,包括抗体依赖性细胞介导的细胞毒性(ADCC)。每种测定都整合了犬Fcgamma受体并采用荧光素酶报告基因,提供灵敏、定量且可重复的读数,适用于效力和MoA评估。此外,还开发了基于细胞的报告基因生物测定,以测量调节犬免疫检查点(PD-1/PD-L1)或共刺激受体(CD40)的抗体的效力。作为对这些基于细胞工具的补充,改进的犬抗体结合测定为表征抗体-靶点相互作用提供了一种快速、均相的替代方案,可取代ELISA和SPR方法。该测定支持从筛选到兽医抗体治疗药物效力放行测试的抗体开发。总之,这些发光测定平台简化了兽医免疫肿瘤学研究,加速了治疗性抗体的跨物种转化。
查看英文原文 English abstract
Advances in immuno-oncology increasingly depend on translational animal models to inform mechanism of action (MoA), pharmacokinetics, and therapeutic potential. Beyond their preclinical utility for human therapies, these models are critical for developing novel biologics in veterinary oncology, particularly in canine cancers, which share key demographic, immunologic and molecular features with human disease. A major limitation in this research is the lack of robust analytical tools to characterize species-specific antibody function and receptor engagement. We developed a suite of luminescent, cell-based bioassays to quantify Fc-mediated effector mechanisms, including antibody-dependent cellular cytotoxicity (ADCC). Each assay incorporates canine Fcgamma receptors and features luciferase reporters, providing sensitive, quantitative, and reproducible readouts suitable for potency and MoA evaluation. In addition, cell-based reporter bioassays were developed to measure the potencies of antibodies that modulate canine immune checkpoints (PD-1/PD-L1) or co-stimulatory receptors (CD40). Complementing these cell-based tools, an improved canine antibody binding assay offers a rapid, homogeneous alternative to ELISA and SPR methods for characterizing antibody-target interactions. The assay supports antibody development from screening to potency release testing of veterinary antibody therapeutics. Together, these luminescent assay platforms streamline veterinary immuno-oncology research, accelerating translation of therapeutic antibodies across species.
利益披露 Disclosure
J. Wang, None.. D. Garvin, None.. I. Kasza, None.. J. Hartnett, None.. M. Cong, None.. J. Grailer, None.

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