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This is a combination immunotherapy consisting of two components: - **NKG2D CAR-NK** refers to natural killer (NK) cells that have been genetically engineered to express a chimeric antigen receptor (CAR) targeting the NKG2D ligand. The NKG2D receptor recognizes stress-induced ligands on tumor cells, leading to NK cell activation and targeted cytotoxicity against cancer cells. These engineered NK cells can attack a broad range of tumors by recognizing multiple types of NKG2D ligands expressed on malignant or immunosuppressive cells within the tumor microenvironment[6][7]. - **PD-1 antibody** is an immune checkpoint inhibitor that blocks the programmed cell death protein 1 (PD-1) pathway, thereby preventing tumor-induced inhibition of immune responses. By blocking PD-1, these antibodies restore or enhance the activity of immune effector cells—including NK and T-cells—against tumors. The rationale for combining these therapies is based on evidence that after infusion into patients or in the presence of tumor microenvironments, NK or CAR-NK cells may upregulate PD-1 expression, which can limit their anti-tumor efficacy. The addition of a PD-1 blocking antibody aims to overcome this adaptive resistance mechanism and further potentiate anti-tumor immunity[3][6]. This combination has been explored in early-phase clinical trials for various advanced solid tumors and hematological malignancies[3][2].
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