Organoid-T-cell co-cultures for preclinical testing of adoptive cell and cancer immunotherapy.

Abstract Recent advances in cancer immunotherapy had a positive impact on the life expectancy of patients with a large 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. Challenges range from lack of confidence in animal cancer models, inter-tumor heterogeneity and the absence of cellular microenvironment. Hubrecht Organoid Technology (HUB) offers an innovative alternative, build on the discovery that adult stem cells proliferate and organize into three-dimensional organotypic structures when they are embedded into Matrigel. HUBOrganoids™ are generated from healthy and disease tissues and stored as “living” biobanks with high quality and reproducibility. HUB Organoids recapitulate complex characteristics of the original parental tissue, including molecular heterogeneity, and morphological and functional traits. HUB has developed organoid-T-cell co-culture systems that allow a physiologic representation of the complexity of interactions in the tumor microenvironment, which is important for evaluating the effects of novel therapies. HUB offers an innovative platform combining image-based analysis with flow cytometry to visualize and quantify T-cell-tumor interactions as well as measurements of T-cell cytotoxicity against tumor (and normal-matched) organoids for colorectal and several other cancers. Our platform offers a powerful strategy for the development and validation of cancer immunotherapy and may help to screen the efficacy of immune checkpoint blockade or bispecific antibodies. In addition, cancer organoid-T-cell co-culture may also predict the functionality of tumor-infiltrating lymphocytes (TIL) and chimeric antigen receptor (CAR)-engineered T cells. As such, our platform offers opportunities in preclinical development and could become a diagnostic tool to predict individual patient response to immunotherapy. Citation Format: Pleun Hombrink, Soura Mardpour, Ewout Spaan, Jarmil Hanrath, Farzin Pourfarzad, Jasper Mullenders, Rene Overmeer, G.J Robert, Vries, F Sylvia, Boj. Organoid-T-cell co-cultures for preclinical testing of adoptive cell and cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2977.