关键词: NCG小鼠, 免疫系统人源化, Hu-PBL模型, 临床前动物模型

Abstract:

To improve the construction success rate of the mouse model with humanized immune system and provide preclinical animal model for further research on tumor immunotherapy drugs， the methods and techniques of the mouse model with humanized immune system construction were explored. The mouse model with humanized immune system was established by injecting HuPB-MNC cells with different numbers and five donors into tail vein of severely immunodeficient mice NCG. The body weight and mortality were recorded twice a week； on the 7^th， 14^th， 21^st， 28^th， 35^th day of the experiment， blood were collected from orbital venous plexus， and the human CD45⁺ T cells reconstruction level in NCG mice peripheral blood was detected by flow cytometry. The level of CD45⁺ T cells in peripheral blood of NCG mice increased gradually with the time after injection， and reached more than 25% at about 3~4 weeks. The results showed that， the construction of the mouse model with humanized immune system should consider the construction method， the strain， sex and feeding of immunodeficient mice， the donor， number and cell state of immune cells. Strategies such as overcoming the differences by adopting multiple donors， and maximizing the window period by optimizing tumor model and immune cell donor combined inoculation plan， which can improve the success rate of model construction and application conversion rate， further improve the construction method of the mouse model with humanized immune system in laboratory， and provide a more favorable drug development tool for tumor immunotherapy.

Key words: NCG mice, humanized immune system, Hu-PBL model, preclinical animal model