Abstract 2831: Development and application of the NCG-hIL2 mouse model: A humanized platform for enhanced NK cell evaluation in ADCC efficacy testing

Abstract Natural Killer (NK) cells play a pivotal role in immune surveillance and antitumor responses, making them valuable targets in cancer immunotherapy. The assessment of therapeutic antibodies' efficacy, particularly in the context of Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC), necessitates models that faithfully recapitulate human NK cell responses. Here, we introduce the NCG-hIL2 mouse model, designed to address these requirements and advance our understanding of NK cell development. The NCG-hIL2 mouse model was engineered to express human Interleukin-2 (IL2) cytokine, a critical factor in NK cell development and activation. This humanized platform allows for the robust reconstitution of human NK cells through the transplantation of peripheral blood mononuclear cells (PBMCs) or hematopoietic stem cells (HSCs). In this study, we validate the NCG-hIL2 model's exceptional capability in supporting the reconstitution of human NK cells, highlighting the indispensable role of IL2 in NK cell development. Moreover, we demonstrate its utility in the evaluation of therapeutic antibodies, specifically Trastuzumab and the ADCC-enhanced Margetuximab, in the context of ADCC efficacy testing. Our findings reveal that the NCG-hIL2 model provides a unique advantage for assessing the impact of IL2 on NK cell development, thus facilitating a deeper understanding of the complex interplay between NK cells and therapeutic antibodies. The NCG-hIL2 mouse model serves as a valuable tool for studying NK cell development and evaluating the efficacy of immunotherapies, particularly in ADCC. By reconstituting human NK cells and leveraging the role of IL2, this model offers an enhanced platform for preclinical evaluation of therapeutic antibodies, ultimately advancing our ability to harness NK cell-mediated antitumor responses. It is poised to contribute significantly to the field of cancer immunotherapy and drug development. Citation Format: Yuan Fang, Hongyan Sun, Huiyi Wang, Jun Xing, Jialu Fan, Jing Zhao, Xiang Gao, Cunxiang Ju. Development and application of the NCG-hIL2 mouse model: A humanized platform for enhanced NK cell evaluation in ADCC efficacy testing abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 2831.