PO.IM02.07 · 免疫学
缺乏FcgammaR的HIS模型提供更高的可预测性并有助于免疫肿瘤学治疗药物评估的研究设计
HIS models lacking FcgammaR provide increased predictability and facilitate study design for evaluation of immuno-oncology therapeutics
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
支持持久人NK和T细胞功能的人源化免疫系统（HIS）小鼠平台对于评估CAR-NK和CAR-T疗法至关重要。残留的小鼠Fcγ受体（FcgammaRs）可干扰对基于IgG的治疗药物和工程化细胞产品的解读。我们比较了植入人NK细胞的hIL-15 NOG小鼠和FcgammaR缺失的FcResolv™ hIL-15 NOG小鼠，观察到相当的≥12周持久性和稳定的CD56⁺CD16⁺谱，可用于延长的工程化细胞研究。在CD34⁺ HIS肿瘤模型中，仅在FcResolv™小鼠中准确检测到抗PD1的疗效和药效学。FcgammaR缺失的HIS平台改善了对CAR-NK/CAR-T疗效、迁移和脱靶反应的预测性评估。
查看英文原文 English 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 (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.
利益披露 Disclosure
M. Buczek, None..
P. Dube, None..
N. Smith, None..
L. Baskin, None..
E. Andino, None..
D. Freer, None..
K. Bott, None.