Abstract 4612: Development of an Integrated Microfluidic Chip for CAR T-Cell Therapy: A Preclinical Trial-on-Chip Tool

Chimeric antigen receptor (CAR) T-cell therapy has demonstrated promising outcomes in treating leukemia, yet it confronts significant hurdles due to severe side effects like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Furthermore, existing preclinical evaluation platforms often fall short in accurately replicating the human tumor microenvironment, leading to extended development durations and elevated costs. To overcome these challenges, we have developed an innovative, integrated microfluidic chip equipped with microarchitectural features that precisely mimic tumor niches, thus enhancing the modeling of CAR T-cell therapy. This chip incorporates an integrated biosensor for real-time cytokine detection, providing essential insights into cytokine dynamics throughout the therapy process. This advanced chip enables spatiotemporal monitoring of CAR T-cell functionality by observing key processes such as T-cell extravasation, target recognition, and leukemia cell destruction. Additionally, it supports the detailed examination of immune cell interactions, including those with monocytes and basophils, which are critical for understanding the side effects of CAR T therapy, particularly its impact on neuronal tolerance. By meticulously tracking these dynamics, our tool not only refines the precision of therapy modeling but also deepens our understanding of the immune response and potential toxicities associated with CAR T-cell therapy. Our investigations using the chip have yielded detailed profiles of cytokine levels across various therapy phases, including remission, resistance, and relapse. Moreover, the chip is capable of evaluating the effects of compounds in inhibiting cytokine release. This cutting-edge tool significantly shortens the development timeline, reduces costs, and enhances the physiological relevance of preclinical evaluations for CAR T-cell therapy. The implementation of this ‘(pre-)clinical-trial-on-chip’ platform is poised to revolutionize CAR T-cell therapy by facilitating the development of personalized therapies and informing clinical decision-making processes. Our findings represent a transformative step forward in the optimization and safety profiling of CAR T-cell therapies. Citation Format: Xuejia Kang, Lang Zhou, Weiqiang Chen, Zongliang Yue, Pengyu Chen. Development of an Integrated Microfluidic Chip for CAR T-Cell Therapy: A Preclinical Trial-on-Chip Tool [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 4612.