In our preclinical studies 8H8_SDIE specifically binds to CD276 on NSCLC cell lines, resulting in significant NK cell activation, characterized by increased expression of CD69 and CD107a, and the secretion of cytotoxic mediators such as IFNγ, perforin, and granzyme B. These findings suggest that 8H8_SDIE may provide a novel therapeutic option for patients with CD276-positive NSCLC, particularly those who have failed to respond to conventional T cell-activating ICIs. The gene discussed is CD69; the disease is non-small cell lung carcinoma.