Abstract 4257: A novel 3D co-culture platform for patient-specific immune-oncology treatment

Abstract

Abstract Lung cancer is the leading cause of global cancer-related mortality resulting in ~1.8 million deaths. annually. Over the past decade, the contribution of tumor microenvironment (TME) in lung cancer progression has been highly appreciated and provided significant improvements of survival outcomes for patients. That includes the complexity of the tumor immune microenvironment (TIME) playing a critical role in cancer progression. However, drug resistance usually arises and there is an urgent need for novel immune cell-based therapies. 3D tumor cell structures that recapitulate the architecture and functionality of the original tumor have revolutionized the understanding of disease mechanisms and testing potential therapeutics. However, there are certain drawbacks that need to be overcome. For example, these models mainly consist of only the epithelial compartment and lack signals from the microenvironment. Recent advances with engineering co-culture systems with immune cells at Champions Oncology help to emulate cell-cell and immune cell infiltration. We have successfully established a biobank of TumorGraft3D (CTG3Ds) derived from non-small cell lung cancer (NSCLC) patient-derived xenografts as well as their autologous and allogeneic immune cells (TILs, PBMCs) to establish a proprietary co-culture platform to investigate disease mechanisms and test potential therapeutics. In brief, surgical resections from patients were used to generate patient-derived xenografts organoids, and matched immune cells were expanded using standard rapid expansion protocol. The combination of a comprehensive staining system and high-content imaging as an endpoint allowed for 3D confocal analysis and deep evaluation of cancer-immune cellular interaction at the single cell level. Our pipeline of image analysis not only differentiates cancer-immune cell spatial distribution and cellular death but also allows for the evaluation of tumor infiltration and drug cytotoxicity. The characterization of the platform showed proliferation of the cancer cells and functional immune profiling by flow cytometry. The molecular profile of the organoids composing the platform showed a tight overlap with the original tumor highlighting the clinical relevance of the model. In addition, this novel co-culture platform has been tested with several NSCLC models to test the efficacy of various therapeutics such as immune-checkpoint inhibitors (ICIs) in reproducible, cost-effective, and patient-specific manner. In summary, Champion’s novel co-culture platform allows screening of novel immune targeting agents to determine impacts tumor cytotoxicity. Furthermore, our lung cancer tumorGraft3D platform serves as a powerful tool to facilitate the practice of precision medicine by investigating a variety of therapeutic modalities, alone or in combination, to identify patient-specific treatment strategies. Citation Format: Taylor Light, Samaneh Kamali, Mara Gilardi, Abhay Andar, Karin Abarca-Heidemann, Maria Mancini. A novel 3D co-culture platform for patient-specific immune-oncology treatment [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 4257.