Depletion of an immature cord blood NK subset reverses trogocytosis-driven CAR NK dysfunction.

Removing an immature cord blood NK cell subset improves CAR NK cell function by preventing trogocytosis-driven dysfunction, enhancing tumor targeting.

• Why it matters: Donor variability hampers the consistency of CAR NK cell therapies, and understanding the cellular mechanisms behind this variability is crucial for improving treatment outcomes.
• What they did: The study analyzed cord blood-derived CAR NK cells, identifying a specific immature subset (DN) linked to poor responses, and tested the effects of depleting this subset during manufacturing.
• The result: Depleting the DN subset eliminated trogocytosis-related antigen sinks, restored effective tumor targeting, and improved persistence and efficacy of CAR NK cells across multiple cancer models.