HIS models lacking FcgammaR provide increased predictability and facilitate study design for evaluation of immuno-oncology therapeutics

Humanized immune system (HIS) mouse platforms that support durable human NK and T cell function are essential for evaluating CAR-NK and CAR-T therapies. Residual murine Fc gamma receptors (FcgammaRs) can confound interpretation of IgG-based therapeutics and engineered cell products. We compared hIL-15 NOG and FcgammaR-null FcResolv™ hIL-15 NOG mice engrafted with human NK cells and observed equivalent ≥12-week persistence and stable CD56⁺CD16⁺ profiles, enabling extended engineered-cell studies. In CD34⁺ HIS tumor models, anti-PD1 efficacy and pharmacodynamics were accurately detected only in FcResolv™ mice. FcgammaR-null HIS platforms improve predictive assessment of CAR-NK/CAR-T efficacy, trafficking, and off-target responses.