Reconstructed mouse model of human immune system in PBMC

　　Key words, humanized immune system, PBMC, mouse, tumor immunotherapy drug, human tumor model

　　Peripheral blood mononuclear cells (PBMC) from healthy or tumor patients reconstructed functional humanized T lymphocytes in mice. Therefore, it can be used to evaluate the efficacy of T lymphocyte related immunotherapy drugs.

　　(Figure, PBMC humanized immune system reconstituted mouse model, FLOW cytometry of CD4, CD8, Treg and IFNγ)

　　Non-t lymphocytes, such as DC, macrophages, NK and B, were unable to be reconstructed in humanized immune system reconstituted mice with routine intravenous PBMC inoculation. Therefore, it is not suitable for the study of other immunotherapy drugs for lymphocytic related tumors.

　　The difficulty of PBMC humanized immune system reconstruction lies in the stability of the model:

　　● Human PBMC inoculation can cause GVHD, making the administration window too narrow.

　　● Antagonism between PBMC of different donors and tumor cells is different in intensity. Severe antagonism will lead to immune system reconstruction or tumor growth stability reduction, or even the failure of reconstruction.

　　● There is a strong difference between the PBMC of different donors, and the pharmacodynamic response is different under the condition that the tumor cells and the drug remain the same, resulting in poor reproducibility of pharmacodynamic trial.

　　To solve the stability and repeatability problems of the PBMC model, The model Creation biology (Strain, Select, Supervise, Storage) experiment strategy comprehensively improves the traditional PBMC model.

　　After inoculation with the same PBMC donor, THE GVHD of NIG mice with independent intellectual property rights could be extended by 2 weeks compared with conventional NSG mice.

　　Based on the deep exploration of PBMC model modeling, Model Biology created a four-level screening method, which greatly improved the success rate of PBMC efficacy trials by screening PBMC donors for their reconstruction ability, GVHD, compatibility with different tumor cell lines, and compatibility with tested drugs in vitro and in vivo.

　　In the course of the study, PBMC reconstruction was continuously monitored in each mouse, providing first-hand evidence to eliminate data interference in mice without immune system reconstruction. Thus increasing the interpretability of the experimental results.

　　The PBMC of the same donor will be backstored to provide customers with PBMC of the same donor for repeated or continuous tests, so as to ensure the consistency of the test.

　　(Case data chart)

　　Invasive organisms can not only apply PBMC humanized immune system reconstruction model to human tumor cell line allograft model (CDX), but also further combine it with human tumor allograft model (PDX) to establish PDX model with humanized immune system. To provide a cost-effective and reliable model for effectively predicting the clinical effectiveness of immunotherapeutic drugs.

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