Abstract

Background

The reconstitution of a fully functional human immune system in the NCG mouse (hu-NCG) provides a unique opportunity to assess the efficacy of new drug candidates acting on human immune cells such as T cells, myeloid cells and NK cells. Enhanced NCG mice have been further developed to boost the differentiation of myeloid and NK cells, allowing scientists to efficiently test new antibodies or small molecules targeting these immune cell populations.

Methods

A fully functional human immune system has been reconstituted in NCG mice after the transplantation of CD34+ human stem cells (hu-NCG model). Then, cell-line derived xenografts (CDX) and patient derived xenografts (PDX) have been engrafted in the hu-NCG model. The tumor growth has been monitored and the immune response assessed by flow cytometry.

Results

We observed infiltration of human immune cells in the tumors. Furthermore, checkpoint inhibitors such as anti-PD1 strongly reduced tumor growth in hu-NCG demonstrating the potency of this model in onco-immunology. Alternatively, we demonstrated that hu-NCG, immunized against cancer antigens elicits strong T cell response as well as IgG production.

Conclusion

Collectively, the huNCG mouse model demonstrats its relevance for the preclinical testing (Mono and Combo therapies) of drugs in immuno-oncology.

Legal entity responsible for the study

The authors.

Funding

Transcure Bioservices.

Disclosure

All authors have declared no conflicts of interest.

中文翻译：

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116P开发用于免疫肿瘤学的临床前研究的高级人类免疫系统小鼠模型

抽象的

背景

NCG小鼠（hu-NCG）中功能齐全的人体免疫系统的重建为评估作用于人类免疫细胞（例如T细胞，髓样细胞和NK细胞）的新候选药物的功效提供了独特的机会。增强型NCG小鼠已得到进一步开发，以促进骨髓和NK细胞的分化，从而使科学家能够有效地测试针对这些免疫细胞群的新抗体或小分子。

方法

CD34 +人干细胞（hu-NCG模型）移植后，已在NCG小鼠中重建了功能齐全的人免疫系统。然后，已将细胞系衍生的异种移植物（CDX）和患者衍生的异种移植物（PDX）移植到hu-NCG模型中。已经监测了肿瘤的生长，并通过流式细胞术评估了免疫应答。

结果

我们观察到人类免疫细胞在肿瘤中的浸润。此外，检查点抑制剂（例如抗PD1）在hu-NCG中大大降低了肿瘤的生长，证明了该模型在肿瘤免疫学中的潜力。或者，我们证明了针对癌症抗原免疫的hu-NCG引发了强烈的T细胞反应以及IgG产生。

结论

总体而言，huNCG小鼠模型证明了其与免疫肿瘤学药物临床前测试（单药和组合疗法）的相关性。

负责研究的法人实体

作者。

资金

Transcure生物服务。

揭露

所有作者均声明没有利益冲突。