Abstract 2696: Tumor organoid and immune cells co-cultures to study myeloid cells-targeting immunotherapy

Abstract Cancer immunotherapy is one of the main pillars of oncology treatment due to the clinical success of approaches that enhance anti-tumoral T cell responses. Nonetheless, many patients do not benefit from these approaches, highlighting the need to develop novel immunomodulatory strategies. Exploiting the anti-tumor capacity of innate immune cells is a promising approach that can overcome specific limitations of T cell-targeting therapies and complement existing immunotherapies. Still, promising therapeutic developments face hurdles in translating preclinical findings into treatment since conventional 2D cancer models hold low clinical predictive value. HUB developed an innovative alternative, building on the discovery that adult stem cells proliferate and organize into three-dimensional organotypic structures. Patient-specific organoids are generated from healthy and disease tissues and recapitulate complex characteristics of the original parental tissue, including molecular heterogeneity and morphological and functional traits. To assess the efficacy of therapies that engage innate immune cells, we developed an assay in which organoids derived from colorectal (CRC) or breast cancer patients are co-cultured with PBMC-derived macrophages or monocytes to evaluate the cytotoxic potential of exogenously activated myeloid cells. We tested the ability of macrophages to phagocyte human CRC organoid cells in response to anti-CD47 antibody. The pro-phagocytic function of anti-CD47 was detected by several methods (i. e. , flow cytometry, imaging), indicating the platform's suitability to evaluate ADCP-modulating compounds. Moreover, to assess whether our PBMC-organoids co-culture platform is suited to detect monocyte-mediated effects, Lipopolysaccharide (LPS) plus IFN-γ were used to activate monocytes in the co-culture assays. We observed an increase in cytokines secretion (i. e. , CXCL10), immune cell activation and organoid killing, indicating that our assay allows the detection of monocyte activation through different types of readouts. In summary, our organoid-immune cell co-culture platform allows to study the response of tumor organoids to innate immune cells, holding significant value for the preclinical development of immunotherapies based on innate immune cells. Citation Format: Lorenzo Spagnuolo, Francisco Morales-Rodriguez, Alessandra Merenda, Cesar Oyarce, Farzin Pourfarzad, Robert G. Vries, Sylvia F. Boj. Tumor organoid and immune cells co-cultures to study myeloid cells-targeting immunotherapy 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 (6Suppl): Abstract nr 2696.