huHSC-NCG-hIL15

Wild Mouse 750
Wild Mouse 750
Human Xenograft Models
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Autoimmune Disease Models
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Obesity ModelsDiabetes ModelsNon-alcoholic Steatohepatitis (NASH) ModelsHyperlipidemia ModelsOsteoporosis ModelsHyperuricemia Models
Humanized Immune System Models
huPBMC-NCGhuHSC-NCG-XhuHSC-NCG-hIL15huHSC-NCG
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Wild Mouse 765
Wild Mouse 765
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Immuno-Oncology Mouse Models
Human Xenograft ModelsHumanized Immune Checkpoint ModelsHumanized Immune System ModelsSpontaneous Tumor Models

Interleukin-15 (IL15) is a pleiotropic cytokine produced by activated monocytes, including macrophages, epidermal cells, and fibroblasts, exhibiting biological activity similar to IL2. IL15 can activate and mediate the proliferation and survival of T cells, B cells and NK cells. By knocking in humanized IL15 in an NCG mouse model, GemPharmatech produced the next-generation NCG-hIL15 strain, which promotes the colonization and activity of human-derived NK cells. To obtain the huHSC-NCG-hIL15 model, human hematopoietic stem cells (CD34+HSC) are transplanted into NCG-hIL15 mice.

 

The lifespan of huHSC-NCG-hIL15 is more than 36 weeks making huHSC-NCG-IL15 mice an ideal animal model to evaluate the efficacy of human anti-tumor antibodies based on T cells and NK cells.

 

Applications

  • Engraftment of human-derived tumors for the screening of relevant drugs, especially for the evaluation of drug efficacy based on ADCC effects.

  • Cell derived xenograft (CDX), Patient derived xenograft (PDX) models requiring an immunocompetent human immune system in mice

  • Human hematopoietic and immune system research

 

Supporting data

1. hIL15 expression in peripheral blood of NCG-hIL15 mice

图片1.png

The expression of human-derived IL15 was detected in both heterozygotes and homozygotes of NCG-hIL15 mice, with higher expression levels in homozygotes.


2. Immunophenotypes of huHSC-NCG and huHSC-NCG-hIL15 mice

图片2.png

Flow cytometry was used to determine the reconstitution level of each immune cell in the peripheral blood of huHSC-NCG and huHSC-NCG-hIL15 mice at 7, 9, 11, and 13 weeks of birth. The detection indexes were hCD45, hCD3, hCD19, hCD4, hCD8, hCD56. The level of hCD45+ cells reached levels over 20% 5 weeks after inoculation. Meanwhile, hCD3+ T cells gradually increased and developed hCD4+T and hCD8+T subpopulations. Compared with huHSC-NCG mice, CD56+NK cells displayed higher reconstitution levels.


3. Function of NK cells in peripheral blood of huHSC-NCG and huHSC-NCG-hIL15 mice

图片3.png

The NK cell functional proteins was characterized at week 13 post engraftment. Peripheral blood sample was taken from huHSC-NCG and huHSC-NCG-hIL15, stained with CD56, CD16, KIR3DL and NKG2D, and analyzed by flow cytometry. Compared with huHSC-NCG, the humanization of NK cell reconstruction levels increased significantly in huHSC-NCG-hIL15 mice, and the functional proteins KIR3DL and NKG2D were also detected.


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