Establishing a vascularized 3D tumor model with an engineered endothelial–tumor interface that facilitates testing of cellular immunotherapies
The development of predictive and scalable preclinical testing platforms for cellular immunotherapies is critical to accelerate translation and improve therapeutic efficacy in solid tumors. My project focused on the development and validation of an advanced vascularized 3D tumor model to support the evaluation of cellular immunotherapies, particularly in urothelial carcinoma and small cell lung cancer (SCLC) — malignancies with high unmet clinical need and limited immunotherapy options. To address limitations of conventional systems, an alternative in vivo tumor model was established that more accurately recapitulates tumor architecture, cellular heterogeneity, tumor vascularization, immune cell migration and immune–endothelial cell interactions.
The platform was validated using a CD276 (B7-H3)–targeting T cell engager (TCE). CD276 is a promising cancer immunotherapy target due to its high expression across multiple solid tumors and restricted expression in normal tissues, making it well suited for targeted immune cell engagement. Functional validation demonstrated the utility of the model for assessing intratumoral immune cell infiltration and activation.
The project integrated a range of advanced methodologies, including multicolor flow cytometry for immune phenotyping, two-photon microscopy for spatial and functional analysis within tumor models, and RNA sequencing to characterize transcriptional responses
