Human epidermal growth factor receptor 2–Natural killer group 2 member D–Cluster of differentiation 16 (HER2–NKG2D–CD16) (HER2–NKG2D–CD16)

HER2–NKG2D–CD16 refers to a trispecific therapeutic engagement strategy designed to harness the innate immune system against HER2-expressing malignancies. This approach utilizes a multi-specific agent, such as a TriNKET (Trispecific NK cell Engager Therapy), to simultaneously bind the Human Epidermal Growth Factor Receptor 2 (HER2) on tumor cells and two potent activating receptors, NKG2D and CD16, on Natural Killer (NK) cells (Dragonfly Therapeutics, 2023). By co-engaging these receptors, the therapy facilitates the formation of an immunological synapse between the NK cell and the cancer cell, bypassing traditional inhibitory signals and inducing robust tumor cell lysis (Demaria et al., 2021). This mechanism is intended to enhance the efficacy of HER2-targeted therapy, particularly in patients who have become resistant to standard monoclonal antibodies like trastuzumab. Clinical development is currently focused on treating advanced solid tumors, including breast, gastric, and lung cancers, where HER2 is overexpressed (NCT03503955).

Other names

HER2-targeted TriNKETHER2/NKG2D/CD16 trispecific NK cell engagerHER2-NKG2D-CD16 complexDF1001 target profile

Simultaneous engagement of HER2 on tumor cells and NKG2D/CD16 on NK cells to induce targeted tumor cell lysis via NK cell activation (Dragonfly Therapeutics, 2023; NCT03503955).