Monalizumab

Monalizumab is a humanized monoclonal antibody that targets NKG2A, an inhibitory receptor on natural killer (NK) cells and some CD8+ T cells. It was developed by Innate Pharma and has been studied in oncology, including collaborations with AstraZeneca.

By blocking the NKG2A–HLA-E interaction, monalizumab aims to release inhibitory signals on NK cells and CD8+ T cells, promoting anti-tumor immunity. This enhancement can augment the effects of other anti-tumor antibodies that recruit NK cells via antibody-dependent cellular cytotoxicity, such as cetuximab, and may synergize with PD-1/PD-L1 inhibitors.

Monalizumab has been evaluated in multiple solid tumors, most prominently in combination with cetuximab in head and neck squamous cell carcinoma, and in combination with anti–PD-L1 agents in other studies. As of 2024, it remained investigational and had not received regulatory approval from major authorities.

It is administered by intravenous infusion in clinical trials. Reported adverse events across studies have included infusion-related reactions, fatigue, rash, and diarrhea, with a safety profile consistent with monoclonal antibody therapies. Immunotherapy-related immune-mediated adverse events have been monitored in trials.

Research continues to define which patient populations and combinatorial regimens yield the most meaningful clinical benefit, and to characterize biomarkers predictive of response to NKG2A blockade.