Abstract 3704: A semiconductor-based biosensor for sensitive T cell detection and common neoantigen identification in cancer immunotherapy

Abstract Background: Identifying common neoantigens and detecting T cell responses to these antigens are critical for providing therapeutic targets and monitoring treatment efficacy. However, current cancer targeted sequencing panels miss up to 95% of genes corresponding to immunogenic neoantigens, limiting treatment options. Detecting specific T cells responsive to these neoantigens is also challenging due to their low abundance and limitations of existing detection methods. Objective: We developed an innovative extended-gate field-effect transistor (EG-FET) biosensor for sensitive detection of T cells within heterogeneous immune populations and a comprehensive common neoantigen database to identify widely shared tumor antigens, addressing limitations in molecular profiling and aiding generalized treatment design. Methods: The EG-FET biosensors leverage semiconductor technology for label-free, real-time detection with high sensitivity. Antibodies targeting T cell surface markers were immobilized on the chip, enabling antigen-antibody interactions to differentiate T cells from other immune cells. Its capability to detect multiple samples simultaneously was assessed, maximizing throughput. We developed a common immunogenic neoantigen database using a pipeline that predicts neoantigens from TCGA data and quantifies their prevalence. Results: The biosensor detected and differentiated T cells with high sensitivity and specificity. The platform detected as few as 1,000 T cells, significantly reducing sample requirements compared to traditional methods needing 100,000 cells. Detection was completed in under 30 minutes, decreasing processing time and costs. The ability to detect multiple samples simultaneously enhanced efficiency. The common neoantigen database aids in identifying widely shared tumor antigens, improving generalized treatment strategies and expanding coverage of immunogenic targets missed by current sequencing panels. Conclusion: Combining EG-FET biosensors with a common neoantigen database offers a transformative approach in cancer immunotherapy. By enabling sensitive detection of T cells within heterogeneous immune populations and identifying common neoantigens, the platform addresses tumor heterogeneity and limited treatment options. These advancements pave the way for scalable, efficient, and more effective cancer immunotherapy, offering promising strategies to overcome drug resistance and improve patient outcomes. Citation Format: Po-Yuan Chen, I-Fen Ko, Kuan-Hsing Chen, Wai-Shan Chung, Che-Ming Lin, Yuh-Shyong Yang, Tai-Ming Ko. A semiconductor-based biosensor for sensitive T cell detection and common neoantigen identification in cancer immunotherapy [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 3704.