Abstract 1224: Unlocking the potential of 3D patient-derived tumor microtissues as reliable and scalable <i>in vitro</i> pre-clinical models

Abstract Over the last decade remarkable advances have been made in our understanding of tumor biology’s microenvironment, allowing for the development of innovative drugs. However, the vast majority of oncology drug candidates entering clinical trials often fail due to the lack of clinical efficacy. This high rate of attrition is in large part due to the lack of physiologically relevant, clinically translatable, preclinical models. Indeed, current preclinical models often inadequately reflect tumor heterogeneity and intricate complexities of the tumor microenvironment (TME), which are important determinants of both the sensitivity and the acquired resistance of any tumor. In an effort to tackle both these issues, we developed a robust preclinical model based on 3D patient-derived tumor microtissues. While there are a few 3D in vitro/ex vivo models incorporating primary tumor tissue, such as patient-derived organoids, PDX-derived organoids, and organotypic slice cultures, our 3D InSight™ Primary Tumor platform provides the preserved original patient tumor microenvironment at a scale that no one else is able to offer, thereby making this platform amenable for both screening and validation. This platform also addresses the research field’s challenge of mirroring patient heterogeneity in a plate. We successfully established uniform 3D patient-derived tumor microtissues from fresh surgically resected tissues from colorectal or breast cancer, with a success rate of 70%. The newly formed 3D patient-derived tumor microtissues were characterized physiologically. We were able to accurately identify the cell types comprising the tumor and the TME by flow cytometry after tissue dissociation. Furthermore, these 3D patient-derived tumor microtissues were treated with standard of care chemotherapeutic drugs, and mimicked the in vivo response which we would expect to see with the same original tumor. Therefore, our 3D InSight ™ Primary Tumor platform is a solution that allows for the testing of multiple therapeutics as single agents/combinations, in a model that very closely resembles its in vivo counterpart. The ability to do this at scale has never previously been offered on any platform. Furthermore, this platform will pave the way for the development of therapeutics in oncology that are truly tailored to specific patient profiles, thereby greatly improving the prognosis and quality of life for patients suffering from cancer. Citation Format: Laure-Anne Ligeon, Charlotte Veser, Michal Rudnik, matthias Zbinden, Agnieszka Pawlowska, Simon Hutter, Tala Issa, Irina Agarkova, sue grepper, Nils Goedecke, Madhu Nag. Unlocking the potential of 3D patient-derived tumor microtissues as reliable and scalable in vitro pre-clinical models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1224.