Abstract 6491: Advancing precision oncology: Integrating AVI-PDX and patient-derived organoid technologies for enhanced preclinical modeling in immuno-oncology

Abstract The AVI-PDX platform enables the creation of miniature, patient-specific tumor models within living organisms, specifically avian embryos. We have developed next-generation, humanized models that incorporate immune cells, expanding the utility of AVI-PDX for investigating immune cell-based therapies and checkpoint inhibitors, both as monotherapies and in combination with standard treatments. Recently, patient-derived organoids have become valuable models for oncology research, offering diverse molecularly characterized resources. However, traditional organoids often lack key components of the stroma and immune microenvironment, limiting their application for studying immune-modulating therapies. To overcome these challenges, we combined AVI-PDX with patient-derived organoid technologies to create an avian patient-derived organoid model, termed AVI-PDO. Here, we describe the generation of a colorectal cancer (CRC) AVI-PDO model.Colorectal tumor organoids from a patient sample were cultured, dissociated, and micro-implanted into avian embryos at established sites within the AVI-PDX model. We conducted a time-course analysis, harvesting embryos 3 to 6 days post-implantation and visualizing them using light-sheet microscopy. Notably, we observed that initially dispersed tumor cells aggregated and reformed 3D organoid-like structures within the embryo. To further characterize these structures, we performed immunolabeling on tissue cryosections, revealing tumor cells organized into spherical formations with central lumens, expressing polarity markers. Additionally, a significant number of Ki67-positive cells were present, indicating active proliferation within these structures. This study demonstrates that our combined AVI-PDX and organoid approach allows the re-creation of organoid-like structures within avian embryo tissues, providing a novel humanized model. This model paves the way for studying immune-based therapies within a whole organism context, offering a comprehensive system that includes systemic signaling and the tissue microenvironment. Citation Format: Clélia Costechareyre, Romain Teinturier, Jürgen Loskutov, Mayrone Mongellaz, Madeleine Nadolny, Marjorie Lacourrège, Loraine Jarrosson, Céline Delloye-Bourgeois, Lena Wedeken, Valérie Castellani. Advancing precision oncology: Integrating AVI-PDX and patient-derived organoid technologies for enhanced preclinical modeling in immuno-oncology [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 6491.