PO.CH01.06 · 化学

ADC在癌症治疗中的应用:基于SPR的发现与表征洞见

ADCs in cancer treatment: SPR-driven insights into discovery and characterization ​

海报缩略图:ADC在癌症治疗中的应用:基于SPR的发现与表征洞见
编号 2408 展板 16 时间 4/20 09:00–12:00 区域 Section 38 主讲 Kristi Riesmeyer, BS
分会场 Antibodies, Antibody-Drug Conjugates, and Nucleic Acids
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作者与单位 Authors & Affiliations

Soraya Diez-Posada1, Cynthia Shuman2, Narashima Murthy Bandaru2, Anna Moberg2, Bryan Edwards1, Sam Ness1, Lowri Davies1, Anja Pomowski1, Laura Bouché1, Isabel Perez-Castro1, Howard Desmond1, Gokhan Yahioglu1, Mahendra P. Deonarain1

1Antikor Biopharma Ltd, Stevenage, United Kingdom,2Cytiva, Marlborough, MA

摘要 Abstract

中文摘要
抗体药物偶联物(ADC)显著推动了癌症治疗的发展。然而,由于肿瘤穿透性差、分子尺寸大以及全身毒性,其在实体瘤中的疗效仍然有限。为应对这些挑战,我们提出了一类新型抗体片段-药物偶联物(FDC),其经过工程改造以改善药代动力学/药效学(PK/PD)特征并增强肿瘤可及性。采用表面等离子体共振(SPR)对多个FDC靶点进行高分辨率动力学和亲和力分析。该方法为合理的候选物筛选和结合动力学优化提供了依据,从而支持了具有优越肿瘤穿透性和治疗潜力的FDC的开发。将SPR数据整合到早期发现工作流程中,在识别具有最佳动力学和亲和力特征的FDC方面发挥了关键作用。在临床前开发中,SPR数据通过精确的结合动力学分析,支持了对FDC安全性和毒理学的评估。SPR数据还加深了我们对靶点生物学的理解,并通过消除对替代抗体的需求降低了开发风险。这种整合方法简化了从发现到临床前评估的过渡,加速了治疗药物的开发。这些发现凸显了FDC作为实体瘤治疗候选物的前景,并为克服传统ADC的局限提供了战略路径。
查看英文原文 English abstract
Antibody-drug conjugates (ADCs) have significantly advanced cancer therapeutics. Yet their efficacy in solid tumors remain limited due to poor tumor penetration, large molecular size and systemic toxicity. To address these challenges, we present a novel class of antibody fragment-drug conjugate (FDC) engineered for improved pharmacokinetic/pharmacodynamic (PK/PD) profiles and enhanced tumor accessibility. Surface plasmon resonance (SPR) was used to perform high-resolution kinetics and affinity analyses across multiple FDC targets. This approach provided rational candidate selection and optimization of binding kinetics, which supported the development of FDCs with superior tumor penetration and therapeutic potential. Integration of SPR data into the early discovery workflow has proven instrumental in identifying FDCs with optimal kinetic and affinity profiles. In preclinical development, SPR data supported assessment of safety and toxicology of FDCs through precise binding kinetics profiling. SPR data also deepened our understanding of target biology and mitigated development risk by eliminating the need for surrogate antibodies. This integrated approach streamlined the transition from discovery to preclinical evaluation, accelerating therapeutic development. These findings highlight FDCs as promising candidates for solid tumor treatment and provide a strategic path to overcome the limitations of conventional ADCs.
利益披露 Disclosure
S. Diez-Posada, None. C. Shuman, Cytiva Employment. N. Murthy Bandaru, Cytiva Employment. A. Moberg, Cytiva Employment. B. Edwards, None.. S. Ness, None.. L. Davies, None.. A. Pomowski, None.. L. Bouché, None.. I. Perez-Castro, None.. H. Desmond, None.. M. P. Deonarain, None.

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