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| http://dx.doi.org/10.1056/NEJMc1903253 | DOI Listing |
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Differences in treatment outcome between translational platforms in developing therapies for gastrointestinal cancers.
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Department of Pharmacodynamics, Medical University of Bialystok, Mickiewicza 2C, 15-222 Białystok, Poland. Electronic address:
The variability in translational models profoundly impacts the outcomes and predictive value of preclinical studies for gastrointestinal (GI) cancer treatments. Preclinical models, including 2D cell cultures, 3D organoids, patient-derived xenografts (PDXs), and animal models, provide distinct advantages and limitations in replicating the complex tumor microenvironment (TME) of human cancers. Each model's unique biological and structural differences contribute to discrepancies in treatment responses, challenging the direct translation of experimental results to clinical settings.
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: Developing ex vivo models that replicate immune-tumor interactions with high fidelity is essential for advancing immunotherapy research, as traditional two-dimensional in vitro systems often lack the complexity required to fully represent these interactions. : In this study, we establish a comprehensive 3D redirect lysis (3D-RDL) assay using colorectal cancer spheroids and adult stem cell-derived, healthy human organoids to evaluate the efficacy and safety profile of , a bispecific antibody targeting carcinoembryonic antigens (CEAs) on cancer cells and CD3 on T cells. This model allows us to assess cytotoxic activity and immune responses, capturing variations in therapeutic response not observable in simpler systems.
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