Abstract 4285: Tumor-on-chip co-culture system: A comprehensive tool in personalized medicine to study cancer progression

Abstract

Abstract As a part of the rapidly advancing organ-on-chip field of research, tumor-on-chip technology (TOC) has emerged as a promising co-culture system to mimic the mechanical and biochemical properties of the tumor microenvironment. This includes factors such as oxygen and nutrient gradients, extracellular matrix stiffness, and cell-cell interactions. Depending on the complexity of system, TOCs are miniature tumor models in a microfluidic chip allowing researchers to gain a better understanding and controlled cancer environment to effectively test potential drug treatments and study immune cell co-cultures. Champions’TumorGraft3D (CTG3D), established from patient-derived xenografts, is the essential component used to recapitulate tumor microenvironment in the TOC platform which provides an even more powerful tool to gain more insight on the efficacy of various therapeutics. Here, we demonstrate the value in combining microfluidic devices with well characterized CTG3D models at Champions Oncology focused on indications including colorectal, breast, gastric and lung cancer. In brief, we optimized cell seeding conditions in both top (seeded with CTG3Ds) and bottom (seeded with endothelial cells) channels to develop TOCs interfacing epithelial-endothelial cells. These established systems may be applied as a baseline for introducing additional cell types such as autologous tumor-infiltrating lymphocytes (TILs) and studying their effect in the presence and absence of additional treatments. With an initial focus on colorectal cancer, we successfully developed TOC epithelial-endothelial interface using CTG3Ds originated from patients with various clinical backgrounds. We measured the permeability as an initial read-out to prove that although tumor cells do not inherently form a tight barrier, they can still form a non-leaky barrier with distinct organoid-like structures. Next, we extended our study to additional indications featuring unique characteristics and proved the feasibility of applying TOCs as a preclinical tool regardless of the tissue-of-origin. In all cases, the endothelial cells formed mature microvascular structures and to confirm the consistency of formed epithelial-endothelial interface among the replicates of each experimental group, we did Luminex studies to prove high consistency in secreted proteins. Regarding the functionality of TOCs, we investigated the effect of relevant test agents to each indication and showed that that the combination of DRAQ7 dye and high-content imaging may be a reliable read-out to detect the response and viability of cancer cells pre- and post-treatment. In summary, our established tumor-on-chip system proves to be a robust and powerful tool for studying the effect of microenvironmental factors in drug testing and immune cells in cancer progression. Citation Format: Samaneh Kamali, Mara Gilardi, Brandon Walling, Abhay Andar, Karin Abarca-Heidemann, Maria Mancini. Tumor-on-chip co-culture system: A comprehensive tool in personalized medicine to study cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4285.