Abstract 4256: Autologous organoids and T cell co-cultures as a powerful personalized platform for immunotherapy development

Abstract

Abstract Recent advances in cancer immunotherapy have had a positive impact on the life expectancy of patients for an extensive range of clinical indications. With new treatment strategies and druggable targets being identified at an increasing pace, the number of patients eligible for cancer immunotherapy is expected to expand steadily. However, promising therapeutic developments face hurdles in translating preclinical findings into therapy since conventional 2D cancer models hold low clinical predictive value. We developed an innovative alternative, building on the discovery that adult stem cells proliferate and organize into three-dimensional organotypic structures when they are embedded into extracellular matrix. Patient-derived organoids are generated from normal and malignant tissues and stored as high-quality biobanks that yield highly reproducible results. HUB Organoids® recapitulate complex characteristics of the parental tissue, including molecular heterogeneity, as well as morphological and functional traits. Since cancer progression and response to immunotherapy are governed by immune cell interactions in the tumor microenvironment, we developed an assay in which colorectal (CRC) and non-small cell lung cancer (NSCLC) tumor organoids are co-cultured with paired tumor infiltrating lymphocytes (TIL) that are simultaneously expanded as a source of tumor reactive cells. Paired resources allow for the screening of immune-modulatory therapies under physiologic conditions, not depending on peptide-pulsing and alloreactivity. We quantify tumor organoid killing and TILs reactivity by combining imaging-based analysis of apoptotic cells with flow cytometry to measure cytokine release by cytotoxic TILs. Here, we show that our system is robust and reproducible with an establishment rate of 75%, allowing for expansion of TILs that preserve T cell receptor repertoires. First line expansion of both PDO and TIL components can be used to effectively build coculture models and probe the tumor and immune components, respectively. Our system offers a powerful tool for the development and validation of cancer immunotherapy and can help to stratify cancer patients for susceptibility to various types of immunotherapies. We certify that the research use of each of the HBS marked above was conducted according to the expectations of each institution. Citation Format: Claudia Beaurivage, BanuPriya Sridharan, Sumeyra Mucuk, Kimberly Nadwodny, Derek Poore, Anna Schepers, Farzin Pourfarzad, Sylvia F. Boj. Autologous organoids and T cell co-cultures as a powerful personalized platform for immunotherapy development [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 4256.