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This is an **investigational combination therapy** consisting of NKR-2 CAR-T cells and 5-azacytidine. - **NKR-2 CAR-T cells** are autologous T-cells genetically modified to express a chimeric antigen receptor (CAR) based on the **Natural Killer Group 2D (NKG2D) receptor**, fused to the CD3 zeta signaling domain. Unlike traditional CAR-Ts that target a single antigen (like CD19), NKR-2 targets multiple NKG2D ligands (MICA, MICB, ULBP1-6) present on 80% of hematologic and solid tumors[1][3][5]. This confers *multi-target tumor cell lysis*, modulation of the tumor microenvironment, reduction of regulatory T-cells and myeloid-derived suppressor cells, enhanced macrophage recruitment, and potential anti-angiogenic effects[1][5]. - **5-azacytidine** is a nucleoside analog and DNA methyltransferase inhibitor (epigenetic modulator) used primarily for myelodysplastic syndrome and acute myeloid leukemia. It can enhance tumor immunogenicity by upregulating antigen expression and reducing tumor-induced immunosuppression. The **combination** is under investigation to evaluate whether 5-azacytidine can improve the efficacy of NKR-2 CAR-T cell therapy by increasing cancer cell susceptibility to immune attack and modifying the tumor environment.
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