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A combination cell and gene therapy composed of bone marrow-derived stromal (mesenchymal) cells engineered to express short hairpin RNA (shRNA) targeting PD-L1 (programmed death-ligand 1). The shRNA suppresses PD-L1 expression on the stromal cells, thus reducing their immunosuppressive impact on immune cells (such as CD4+ T cells) in the tumor microenvironment. This reversal of immunosuppression enhances anti-tumor Th1/Th2 immune responses and inhibits tumor-promoting interactions between stromal cells and malignant cells, as demonstrated in multiple myeloma models. The approach aims to reprogram the tumor microenvironment for improved cancer immunotherapy efficacy[1].
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