HLA-E, a non-classical MHC class I molecule, is frequently overexpressed in tumors, facilitating immune evasion by engaging the inhibitory receptor NKG2A on NK cells and CD8+ T cells. Targeting this axis is crucial for restoring immune activity in both hematologic and solid tumors. To address this, we developed a chimeric NKG2A/NKG2C (A/C) chimeric receptor that combines the high HLA-E affinity of NKG2A with the activating signaling of NKG2C. CD8+ T cells engineered to express the A/C Switch displayed potent cytotoxicity against a broad range of tumor cells expressing high levels of HLA-E and complete tumor control in an orthotopic glioblastoma model (Saetersmoen et al, MED 2024). In NK cells, high endogenous NKG2A expression limits the efficacy of the A/C Switch-based approach due to competition for the ligand. To overcome this, we developed a dual-engineering system combining NKG2A knockout (KO) and A/C Switch integration. Two CRISPR/Cas9-based protocols were compared for NKG2A KO: a short cytokine-driven approach and a feeder-cell-based extended protocol. This comparison evaluated both knockout efficiency and suitability for subsequent viral transduction. Both methods achieved >90% KO efficiency, with post-knockout A/C Switch-transduced NK cells representing >60% of the population. The engineered A/C Switch⁺ NK^NKG2A-KO cells exhibited robust degranulation, pro-inflammatory cytokine secretion, and superior killing of HLA-E-high tumor cells, effectively overcoming immune evasion through the HLA-E checkpoint. These findings establish a rapid and efficient dual-engineering platform, providing an intrinsic check-point converter, combining signaling from the A/C Switch with an unleashed cytotoxic response of NK cells, providing a scalable framework for therapies targeting HLA-E overexpressing tumors.