Abstract 1554: Harnessing the Beacon® optofluidic platform for streamlined discovery of internalizing antibodies

Abstract Antibody drug conjugates (ADCs) are an innovative class of biopharmaceuticals which combine the potency of cytotoxic molecules with the targeted specificity of monoclonal antibodies. The success of a traditional ADC not only hinges on tumor antigen-specific binding but internalization to maximize cytotoxicity from the payload and minimize off-target damage to healthy tissue. The development of an ADC therapy is a complex, multistep process that involves identifying a target antigen, discovering an ideal antibody, selecting the cytotoxic payload and linker, and optimizing the conjugation chemistry - all of which can take years from initial research to therapeutic application. One significant bottleneck within this process is the lack of early phase assays to guide the down-selection of functional antibodies from hundreds of antigen binding clones. Therefore, developing an efficient high-throughput assay for antibody internalization is crucial for accelerating ADC development. The Beacon® optofluidic platform from Bruker Cellular Analysis is an advanced solution for this problem that enables researchers to identify valuable monoclonal antibodies within a week, bypassing the time consuming and laborious process of hybridoma library generation and screening. With this platform, tens of thousands of single primary cells can be isolated using Opto-Electronic Positioning (OEP) technology and assayed for antibody secretion, antigen binding, and receptor-specific internalization in live reporter cells within a single day. This cutting-edge technology is the only platform capable of screening and measuring >10, 000 antibodies simultaneously for rapid internalization (1-2 hours). We showcase the ability to streamline early-phase discovery of internalizing antibodies, going beyond mere antigen specificity to enable high-throughput, real-time evaluation of functional antibodies. The Beacon optofluidic platform significantly reduces hands-on time and resource expenditure, focusing efforts on the most promising ADC candidates for downstream characterization and optimization, ultimately expediting the progression of ideal antibodies into clinical applications. Citation Format: Brittany Benlian, Leqian Liu, Alexander Mastroianni, Minha Park, Vincent Pai, Alireza Salmanzadeh. Harnessing the Beacon® optofluidic platform for streamlined discovery of internalizing antibodies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1554.