Abstract 2408: ADCs in cancer treatment: SPR-driven insights into discovery and characterization.

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. Citation Format: Soraya Diez-Posada, Cynthia Shuman, Narashima Murthy Bandaru, Anna Moberg, Bryan Edwards, Sam Ness, Lowri Davies, Anja Pomowski, Laura Bouché, Isabel Perez-Castro, Howard Desmond, Gokhan Yahioglu, Mahendra P. Deonarain. ADCs in cancer treatment: SPR-driven insights into discovery and characterization abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2408.