(1166-C) Advanced 3D Cell Models for Next Generation Therapeutics: Standardized Organoid Co-Cultures and Assays in Microwell Plates
Tuesday, February 6, 2024
12:00 PM – 1:00 PM EST
Location: Exhibit Halls AB
Abstract: Clinical trials for drug candidates have a high failure rate, often due to disparities between in vitro and in vivo efficacy. Addressing this challenge requires improved cell models that replicate organ-specific biology to identify relevant therapeutic targets.
Organoids, capable of mimicking native tissue complexity, offer a promising solution that recapitulates in vivo physiology in an organ-specific context. However, they present numerous challenges regarding reproducibility, scalability, and analyses. Organoid cultures heavily rely on a solid extracellular matrix (ECM), leading to pronounced size and shape heterogeneity, and imaging difficulties. The organoids are trapped in the ECM and are not equally accessible to other cell types and molecules, hindering the establishment of co-cultures and robust assay development.
Here we present a novel approach to standardize multicellular (co)-cultures: Gri3D®, a ready-to-use platform for high-throughput and reproducible organoid culture. Based on an array of microwells, the platform enables the high-throughput generation of single organoids of precise sizes in suspension-like conditions, and in a single focal plane. The system includes a pipetting port for safe media exchange. It facilitates the assessment of next-generation therapeutics, such as bispecific antibodies, immune modulators, or engineered immune cells, which are in direct contact with organoid models.
We showcase two compelling applications of Gri3D® in assessing next-generation therapeutics. Firstly, its role to study receptor-mediated antibody transcytosis within blood-brain barrier assembloid arrays. Secondly, its utility in evaluating the cytotoxicity of tumor-infiltrating lymphocytes (TILs) and immune-modulators on autologous tumoroids.
The microwell system significantly enhances the efficiency and reproducibility of 3D organoid and co-culture workflows. It integrates with automation and supports a wide range of assays, including traditional whole-well luminescence and fluorescence-based approaches, as well as high-throughput image-based screening assays.