Li et al. identify a specific immature subset of cord blood natural killer cells, defined as CD16− CD161− (DN), that severely undermines the success of CAR NK cell therapy. While mature double-positive (DP) cells provide potent tumor killing, the presence of DN cells triggers a phenomenon called trogocytosis, where these cells strip and accumulate antigen from tumor surfaces. This creates a trogocytic-antigen sink (TAS) that distracts effector cells, leading to self-directed fratricide, metabolic exhaustion, and programmed cell death. Research demonstrates that physically removing these DN cells during the manufacturing process significantly boosts the persistence and anti-tumor activity of the final product. Ultimately, the study offers a practical manufacturing strategy to improve the consistency and clinical efficacy of off-the-shelf immunotherapies.
References:
Li Y, Fan H, Wang G, et al. Depletion of an immature cord blood NK subset reverses trogocytosis-driven CAR NK dysfunction[J]. Cancer Cell, 2026.
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