Abstract

Abstract Advances in the field of immunology and hematopoietic stem cell (HSC) transplantation have prompted the development of murine models that faithfully recapitulate human immune responses. We present the NCG-M/hIL15 model, an innovative advancement in the realm of preclinical research, addressing two key challenges associated with existing models: the limited capacity for human natural killer (NK) cell regeneration in NCG-M and the suboptimal reconstitution of T cells, myeloid lineage cells in NCG-hIL15 mice. Compared to the conventional NCG-M model, the NCG-M/hIL15 model demonstrates a significant improvement in its ability to regenerate human NK cells post-HSC transplantation. This advancement offers a valuable tool for studying NK cell biology, immune surveillance, and antitumor responses. Furthermore, when compared to the NCG-hIL15 model, the NCG-M/hIL15 model outperforms in the reconstitution of human T cells and myeloid lineage cells, contributing to a more comprehensive simulation of human immune responses. The overall survival of mice in this model is notably stable, further enhancing its utility for long-term immunological studies. The NCG-M/hIL15 model not only advances our understanding of human immune responses but also has significant implications for the development of novel immunotherapies and the preclinical evaluation of HSC transplantation strategies. This novel murine model offers a more accurate representation of the human immune system, with the potential to expedite the development of innovative therapeutic interventions. We present this model as a valuable addition to the preclinical research toolkit, promising a deeper understanding of immunology and a brighter future for clinical applications. Citation Format: Huiyi Wang, Jun Xing, Jialu Fan, Yuan Fan, Jing Zhao, Xiang Gao, Cunxiang Ju. Development of a novel murine model, NCG-M/hIL15, for enhanced post-HSC transplantation immunoreconstruction [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(6_Suppl):Abstract nr 118.

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