The huPBMC-NCG mouse model is generated by transplanting Peripheral Blood Mononuclear cells (PBMC) from healthy people into severe immunodeficient NCG mice to construct the human immune system reconstituted mouse model. This model shows fast reconstitution of immune cells, the majority of which are T cells. This system can be used to evaluate the preclinical efficacy of anti-tumor agents. The survival period of huPBMC-NCG mice is 5-7 weeks. Since the reconstitution of T cells is very fast, human T cells recognize and attack mouse tissues causing graft-versus-host disease (GvHD), which also makes this model appropriate for evaluating anti-GvHD drug efficacy. In order to exclude the influence of PBMC from different donor sources on the experimental outcomes, GemPharmatech has established an huPBMC donor library through screening to ensure the stability of huPBMC-NCG immune reconstitution.
hPBMCs were injected through the caudal vein (1x107cells) into NCG mice for huPBMC reconstitution.
Preclinical anti-tumor efficacy studies and safety evaluation
Short-term efficacy evaluation
Evaluation of anti-GvHD drugs
1. The survival curve of huPBMC-NCG
huPBMC from donors F and G were injected into NCG mice, and the survival time was analyzed. Since the implanted PBMC were heterologous immune cells, the huPBMC-NCG mice developed graft-versus-host disease (GvHD), in which the human-derived immune system attacked the mice's tissues and organs, ultimately resulting in death and shortening the application of the huPBMC-NCG mice. In this study, we discovered that mice transplanted with human PBMC died progressively after approximately one month.
2. The human immune reconstitution levels of the huPBMC-NCG mice
Human immune cell levels in peripheral blood of huPBMC-NCG mice were detected by flow cytometry. The levels of human leukocytes and T cells climbed progressively, and by the third week, the mean ratio of human leukocyte had surpassed 50%. Data are shown as Mean±SEM.
Using flow cytometry, the relative amounts of human leukocytes in the spleen, peripheral blood, and bone marrow of huPBMC-NCG mice were measured. Data are shown as Mean±SEM. *P<0.05; **P<0.01; ***P<0.001.