NKG2D CAR NK + NKG2D CAR T cells

This therapy is a **combination of two cell-based immunotherapies**: NKG2D CAR NK cells and NKG2D CAR T cells. Both modalities involve engineering immune cells (natural killer cells and T lymphocytes, respectively) to express a chimeric antigen receptor (CAR) that targets ligands for the activating receptor NKG2D, which are highly expressed on a wide range of tumor cells but minimally present on healthy tissues. - **NKG2D CAR NK cells**: Natural killer (NK) cells are genetically modified with a CAR that uses the NKG2D receptor to recognize and bind to stress-induced ligands on tumor cells, triggering cytotoxic activity. These cells can be administered intraperitoneally and have shown immune modulation and activation of endogenous T cells, as evidenced in early-phase clinical trials for colorectal cancer peritoneal metastases[1][4][3]. - **NKG2D CAR T cells**: T cells are engineered similarly to express a CAR based on NKG2D, enabling recognition and killing of tumor cells through T-cell cytotoxic mechanisms. Clinical studies in malignancies such as acute myeloid leukemia, multiple myeloma, and various solid tumors have demonstrated safety and anti-tumor activity, but persistence and expansion remain challenges[2][5][3][8][10]. - The combination is hypothesized to leverage **complementary immune mechanisms** of both NK cells and T cells for enhanced tumor cell clearance, potentially improving efficacy in cancers where single-agent cell therapies may be insufficient. - Primary indications explored include **solid tumors** (e.g., colorectal cancer with peritoneal metastasis, ovarian, breast, and pancreatic cancers) as well as some hematologic malignancies[1][2][4][5][3]. - As of mid-2025, both modalities are in early clinical and preclinical development, with some ongoing or recently completed Phase I dose-escalation trials.

Other names

NKG2D CAR NK cells + NKG2D CAR T cellsNKG2D chimeric antigen receptor NK and T cells combinationNKG-2D chimeric antigen receptor NK and T cells combinationNKG 2D chimeric antigen receptor NK and T cells combinationNKG2D CAR-engineered NK and T cells combinationNKG-2D CAR-engineered NK and T cells combinationNKG 2D CAR-engineered NK and T cells combination