Abstract 6978: HIS models lacking FcγR provide increased predictability and facilitate study design for evaluation of immuno-oncology therapeutics

Abstract 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 (FcγRs) can confound interpretation of IgG-based therapeutics and engineered cell products. We compared hIL-15 NOG and FcγR-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. FcγR-null HIS platforms improve predictive assessment of CAR-NK/CAR-T efficacy, trafficking, and off-target responses. Citation Format: Monika Buczek, Philip Dube, Nicholas Smith, Janell Richardson, Louise Baskin, Esther Andino, Debra Freer, Kathleen Bott. HIS models lacking FcγR provide increased predictability and facilitate study design for evaluation of immuno-oncology therapeutics abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6978.