Abstract 1986: A novel single-cell CTC platform enables first liquid biopsy for ADC target expression profiling

Abstract Introduction: Despite the expanding landscape of antibody-drug conjugates (ADCs), patient selection remains challenging due to limited liquid biopsy methods for target assessment. Current tissue approaches lack longitudinal assessments and provide insufficient resolution of target expression heterogeneity that could inform ADC selection. We present the first liquid biopsy platform specifically designed for ADC therapy, designed to inform treatment selection through single-cell RNA sequencing of circulating tumor cells (CTCs). This platform provides comprehensive profiling of target antigen expression across multiple ADC targets, establishing the foundation for target expression-based ADC selection. Beyond initial target profiling, this approach could provide a foundation for studying target dynamics and potential resistance mechanisms. Methods: 10 patients with various solid tumors were consented for research from the observational clinical study CTC-M. Blood samples (3x10mL) were collected and processed using either our proprietary platform or a combination of existing commercial instruments. Individual CTCs were barcoded and analyzed via single-cell RNA sequencing to profile expression of multiple ADC targets (including HER2, TROP2, Nectin-4, and c-MET) along with global transcriptome patterns. Patient demographic and disease characteristics were collected in a de-identified database. Results: Single-cell RNA sequencing of isolated CTCs revealed detection of ADC target expression across various cancers. Our fully automated platform delivers barcoded CTCs ready for single-cell sequencing in under 1 hour compared to 6+ hours for existing workflows, integrating both isolation and molecular barcoding steps. The novel isolation technology achieves a 10-100X improvement in CTC purity versus current methods, overcoming a key technological hurdle compared to other systems. The platform maintains plasma integrity throughout processing, enabling simultaneous CTC and ctDNA analysis from a single blood draw. Conclusions: We have developed the first integrated platform enabling rapid, automated preparation of CTCs for single-cell ADC target profiling. Our workflow demonstrates significant advantages in speed, purity, and cost-effectiveness, while enabling concurrent CTC and ctDNA analysis from a single blood draw. This technology establishes the foundation for comprehensive liquid biopsy-based ADC target assessment, addressing a critical unmet need in precision oncology. Citation Format: Antoine Herzog, Xiaokang Li, Mattia Lazzaroni, Salomé Thüler, Sylvie André, Marina Alexandre Gaveta, Stefano Varricchio, Olivier Dubey, Bastien Vergnet, Krisztian Homicsko. A novel single-cell CTC platform enables first liquid biopsy for ADC target expression profiling [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 1986.