A spatially resolved implantable microdevice for multiplexed in situ screening of engineered cellular therapies in...

The clinical translation of cellular immunotherapies for solid tumors remains limited by the lack of adequate tools to evaluate therapeutic function within the native tumor microenvironment. Here, we demonstrate a miniaturized implantable microdevice (IMD) capable of spatially resolving and multiplexing the delivery and screening of multiple T cell therapies directly within live tumors. This customizable IMD is comprised of discrete fibrin-filled reservoirs that can be independently loaded with distinct immune cell formulations, which enables spatially confined release and region-specific immune-tumor interactions within the same tumor mass. Using this platform in glioblastoma xenografts, we simultaneously delivered EGFR-targeting CAR-T cells and control T cells and analyzed adjacent tissues via IHC-based quantitative image analysis and multiplexed immunofluorescence. The perireservoir region adjacent to CAR-T cell reservoirs exhibited dense CD8⁺ infiltration, cleaved caspase-3-mediated apoptosis, and suppressed Ki67 expression, in contrast to minimal activity in control regions. We believe our IMD platform facilitates the parallel in vivo evaluation of multiple immune cell therapies, providing a translational tool to accelerate the development of successful personalized adoptive cell therapies.