CART-NKG2D

CART-NKG2D is an investigational cell therapy in which a patient's own (autologous) or donor-derived T lymphocytes are genetically engineered to express a chimeric antigen receptor (CAR) that incorporates the extracellular domain of the human natural killer group 2 member D (NKG2D) receptor fused to intracellular signaling domains such as CD3ζ and costimulatory domains like 4-1BB. This modification enables the engineered T cells to recognize and bind to multiple stress-induced ligands for NKG2D—including MICA, MICB, and ULBP family members—commonly upregulated on malignant cells but generally absent from healthy tissues. Upon engagement with these ligands on tumor cells, CART-NKG2D mediates direct cytotoxicity and cytokine production independent of native T-cell receptor signaling. Preclinical studies have shown efficacy against various hematologic malignancies (e.g., acute myeloid leukemia [AML], multiple myeloma), solid tumors (e.g., glioblastoma), and cancer stem cell populations. Early-phase clinical trials have demonstrated safety at low doses without dose-limiting toxicities or severe cytokine release syndrome; however, expansion and persistence of these CAR-T products may be limited in vivo[3][5][6][7]. The approach is being developed by academic groups including Dana-Farber Cancer Institute[10].

Other names

autologous NKG2D CAR T cells KD-025CM-CS1 T cellsCM-CS-1 T cellsCM-CS 1 T cells