NK cell immunotherapy has undergone three transformative clinical phases: (1) The cytokine era (2000-2010), where IL-2-activated NK cells achieved 19-27% CR in renal cell carcinoma (RCC) trials; (2) The adoptive transfer era (2010-2020), with haploidentical NK therapy showing 45-58% CR in AML (NCT00990717) (10); and (3) The engineered NK era (2020-present), where CD19-CAR-NK trials demonstrated 73% objective response rate (ORR) with no CRS ≥ grade 3 (NCT03056339) (Marin et al., 2024b). This evidence concerns the gene IL2 and renal cell carcinoma.