General Information

Development

IL15 (interleukin-15) is a pleiotropic cytokine produced by a wide range of cells, including activated monocyte-macrophages, epidermal cells, and fibroblasts, and exerts biological activities similar to those of IL2, with the ability to activate T-cells, B-cells, and NK-cells, and mediate the proliferation and survival functions of these cells ^[1,2]. To this end, we used a transgenic approach in the NPG mouse model to inject the linearized human mIL15p-hIL-15 expression sequence into the prokaryotic nucleus of NPG mice, and screened the obtained progeny for positive mice with the appropriate expression level to produce them as breeders. In an isolator, a commercial hIL-15 NPG mouse strain was established by expansion following inbreeding. Transplantation of human hematopoietic stem cells (HSC) to this mouse results in the formation of HuHSC-hIL15-NPG mice, which are able to rebuild functional T cells and NK cells, and can be used for the study of tumor immunotherapy drugs.

Phenotype

1. Levels of immune cell reconstitution after HSC transplantation in hIL15-NPG mice

Fig1. The levels of peripheral blood immune cells after transplantation of CD34⁺ cell in IL15-NPG mice

Serum were collected from NPG-hIL15 mice with HSC transplantation, compared to HSC-NPG, HSC-hIL15-NPG had a higher hCD56⁺ NK reconstruction level, and a higher subpopulation of differentiated hCD16⁺ NK cells, which remained at a higher level throughout the observed 12 weeks.

HuHSC-NPG-hIL15 Mice Applications

1. Cancer treatment (e.g., lysovirus and CAR-T, etc.)

2. Human hematopoietic system and immune system research

3. Regenerative medicine

4. Infectious diseases

5. Human cell and tissue transplantation

6. NK cell development mechanism research

7. Tumor immunotherapy research on NK cells or NK and T cells combined action

8. Antibody-dependent NK cell-mediated toxicity (ADCC) studies

9.CAR-NK efficacy

Reference

1. Ali AK, Nandagopal N, Lee SH. IL-15-PI3K-AKT-mTOR: A Critical Pathway in the Life Journey of Natural Killer Cells. Front Immunol. 2015, 6:355.

2. Fehniger TA, Suzuki K, Ponnappan A, et al. Fatal leukemia in interleukin 15 transgenic mice follows early expansions in natural killer and memory phenotype CD8⁺ T cells. J Exp Med. 2001, 193(2):219-231.