Abstract 4612: Microphysiological vascularized solid liver tumor model for drug and cell therapy

Abstract

Abstract Development of efficacious therapeutic strategies against solid tumors is limited by the lack of pre-clinical models that can reliably predict treatment outcomes in patients. This is primarily because models often do not accurately reflect the complexity of the tumor microenvironment (TME). The TME consists of vasculature, stromal cells and immune cells that can promote tumor resistance or prevent targeted drug and cell therapy. Here, we developed an in vitro vascularized liver tumor model in a microfluidic device to evaluate drug delivery and immunotherapy approaches. The model consists of a tumor spheroid surrounded by a perfusable self-organized vasculature bed with physiologically relevant permeability. Sorafenib (Nexavar) efficacy was evaluated by assessing tumor spheroid viability, quantified by the loss of fluorescence signal. The presence of vasculature showed enhanced cytotoxicity, highlighting the importance of tumor-vascular interactions for testing therapeutic efficacy. Engineered immune cells (chimeric antigen receptor (CAR) T-cell and transiently expressing T-cell receptors (TCR)) were introduced into the model to demonstrate immunotherapy validation. Our results showed that the engineered immune cells were more effective at infiltrating the tumor spheroid without a vasculature but were more cytotoxic in the presence of the vasculature. By removing the cultured microtissue from the device and performing digital spatial transcriptomics on standard paraffin-embedded sections, we identified known and novel genes involved in creating a pro-tumorigenic microenvironment. This platform can be utilized to model critical features of the in vivo TME, providing better predictability of drug responses, with potential applications towards personalized medicine. Citation Format: Jyothsna Vasudevan, Ragavi Vijayakumar, Jose Antonio Reales-Calderon, Maxine Sin Lam, Jin Rong Ow, Joey Aw, Damien Tan, Giulia Adriani, Andrea Pavesi. Microphysiological vascularized solid liver tumor model for drug and cell therapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4612.