Publications by authors named "M Norkin"
: 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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- Current biomarkers for selecting cancer patients for PD-1 inhibitors, like PD-L1 expression, are often unreliable, particularly in malignant pleural mesothelioma, prompting a search for more effective markers.
- In a study involving 144 patients, researchers analyzed immune cells in tumors to determine their relationship with treatment outcomes and discovered that traditional markers like total CD8+ T cells and macrophage presence did not predict patient survival benefits.
- The study revealed that the presence of PD-1-expressing CD8+ T cells and PD-1-expressing macrophages is an independent predictor of progression-free survival, indicating their potential as valuable biomarkers for immunotherapy success.
Organoids are 3D ex vivo cell aggregates derived from primary tissue and shown to closely recapitulate tissue homeostasis. Organoids deliver certain advantages compared to 2D cell lines and mouse models, especially in drug-screening studies and translational research projects. The application of organoids in the research field is fast-emerging and new techniques for organoid manipulation are constantly developing.
View Article and Find Full Text PDFDespite the remarkable success of immune checkpoint blockade (ICB) therapy, most cancer patients still do not respond. We now find that immunotherapy can induce stem-like properties in tumors. Using mouse models of breast cancer, we observe that cancer stem cells (CSCs) show not only enhanced resistance to T cell cytotoxicity, but that interferon gamma (IFNγ) produced by activated T cells directly converts non-CSCs to CSCs.
View Article and Find Full Text PDFBackground: We propose a new approach for designing personalized treatment for colorectal cancer (CRC) patients, by combining ex vivo organoid efficacy testing with mathematical modeling of the results.
Methods: The validated phenotypic approach called Therapeutically Guided Multidrug Optimization (TGMO) was used to identify four low-dose synergistic optimized drug combinations (ODC) in 3D human CRC models of cells that are either sensitive or resistant to first-line CRC chemotherapy (FOLFOXIRI). Our findings were obtained using second order linear regression and adaptive lasso.