In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 5197-5197
Abstract:
Interleukin 2 is a key molecule that promotes the expansion and activation of lymphocytes, including T regulatory cells (Tregs) and natural killer (NK) cells. Tregs are specialized subpopulation of T cells that suppress the immune response by inhibiting T cell proliferation and cytokine production. NK cells are the predominant innate immune subset that mediates anti-tumor and anti-viral responses. Both Tregs and NK cells are two critical immune cells that play an important role in cancer immunotherapy, however, there is a lack of models that supports the in vivo status of these two immune subsets. To address this, we developed a severe immunodeficient mouse model, NOD/ShiLtJGpt-Prkdcem26Cd52Il2rgem26Cd22/Gpt (NCG-hIL2), by knocking in the human IL-2 gene on the NCG background. The ability of this model to support Treg and NK cells was then compared to NCG and tested with the reconstitution of human peripheral blood mononuclear cells (PBMC) and human hematopoietic stem cells (HSC). In the PBMC engrafted mice, the presence of IL-2 supported the development of T cells, especially the Tregs, with 53.74% in Tregs in NCG-IL2 compared to 4.81% in NCG mice (test at 2 weeks of reconstruction). Similarly, the NK cells are also supported with those cohort engrafted with human HSC (91.63% in NK cells in NCG-IL2 compared to 0.53% in NCG mice, test at 10 weeks of reconstruction). Notably, reconstituted NK cells expressed various NK receptors such as NKp30, NKp44, NKp46, NKG2D, and CD94 in NCG-IL2 mice. They produced comparable levels of granzyme when compared with human peripheral blood-derived NK cells, and a considerable amount of perforin protein was detected in the plasma of huHSC-NCG-hIL2 mice. In conclusion, compared with NCG mice, humanized NCG-hIL2 mice can reconstruct more abundant immune cells and have a wider application in anti-tumor research. It is an ideal model for the preclinical study of anti-tumor therapeutics. Citation Format: Xinxin Zhang, Meirong Wu, Huiyi Wang, Weiwei Yu, Fang Zhu, Jianming Xu, Hongyan Sun, Hongyu Wang, Cunxiang Ju, Santi Suryani Chen, Zhiying Li, Mark Wade Moore, Jing Zhao, Xiang Gao. NCG-hIL2 mice: a novel model to support the development of T regulatory and NK cells. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5197.
Type of Medium:
Online Resource
ISSN:
1538-7445
DOI:
10.1158/1538-7445.AM2023-5197
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2023
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
