Immunodeficient mouse models are important tools across a range of biomedical research fields, including oncology, immunology, infectious disease, stem cell biology, and more. Their availability has advanced mechanistic knowledge of diseases and enabled progress in drug discovery and development. The most recently available model, B-NDG (NOD.CB17-PRKDC.scidIL2RG.TM1./BcgenHsd） - 由生物细胞开发，现在由Envigo许可 - 具有唯一高度的免疫缺陷。B0B体育平台下载下面，我们讨论了B-NDG模型的一些好处，并描述了最近通过其可用性而实现的研究。
The features and benefits of the B-NDG model
B-NDG是通过删除常见的γ链产生的白化物，单基因敲除小鼠（IL2RG.) gene from NOD-scid mice with severe immunodeficiency using CRISPR-Cas9 technology (see the figure below for an illustration of how the B-NDG mouse was generated). The model lacks mature T and B cells or functional natural killer cells and displays a deficiency in cytokine signaling. Therefore, the B-NDG mouse is one of the most immunodeficient models available, and is suitable for engraftment with human hematopoietic stem cells, peripheral blood mononuclear cells, and human tumor cells or tissues.
此外，对人衍生的细胞的最小排斥使B-NDG小鼠的移植的理想宿主（患者衍生的异种移植物）制成理想的宿主。该模型保留肿瘤组织的异质特性，因此精确地重新承载患者特征。
Envigo’s Associate Director of Strategic Marketing, Travis Rothrock, tells us why he is excited about the new availability of this model for research: “The B-NDG can be used to study standard therapies, or to understand how a PDX would grow, for example. But, the real benefit of this model is the option to humanize it, engraft a cell line or a PDX, allow it to grow, and then inject a monoclonal antibody or checkpoint inhibitor to see if they can cause the tumor to shrink over time.”
Characterizing the B-NDG model
Envigo is working with collaborators to fully characterize the B-NDG mouse and compare it with other immunodeficient models. In arecent study, tumor growth was found to be accelerated in B-NDG mice compared to a group of NSGTMmice, which are also highly immunodeficient (illustrated below). The model’s performance in these studies indicate several benefits, described below.
The B-NDG model in action
The features of the model described above increase the likelihood of successful translation from preclinical laboratory work to human efficacy studies. The model has already been used in research to generate CDX and PDX tumor models and human immune system reconstituted models. It has also been used in体内efficacy studies of agents that target immune checkpoints, drug-sensitivity testing, and for optimizing treatments with CAR-modified T cells. Just some of this work is described in more detail below:
+PDX.colorectal model+评估这一点体内efficacy of silvestrol, alone or in combination with oxaliplatin, against colorectal tumors,Chen et al (2019)developed colorectal cancer PDX models by xenografting patient tumor samples into the flanks of B-NDG mice. The study concluded that silvestrol inhibited tumor growth and had a synergistic effect with oxaliplatin to induce apoptosis in PDXs.
+一种开发记忆库T细胞的新策略+Treatment with CAR-modified T cells targeting CD19 has been successful in patients with relapsed/refractory B cell malignancies, but remission occurs frequently. To evaluate whether the activity of CAR-T cells could be maintained,Chen et al., (2020)使用B-NDG小鼠来确定电池如何最佳地重新构作。这导致了提高生存和延迟肿瘤发生。
In summary, the B-NDG immunodeficient mouse offers many benefits compared to other models. The model has been used to successfully establish PDX and CDX models and is well suited for studies that require humanization. In addition, ongoing work to further characterize the model, including the very low levels of PDX rejection, is likely to establish B-NDG mice as a promising research tool capable of successfully recapitulating human diseases.
A more comprehensive list of studies utilizing the B-NDG model, along with a more detailed characterization of the animals, can befound here。If you are interested in using this model in your research,our specialistsare available to discuss your needs. In addition, if you’d like to collaborate with us in characterizing the B-NDG model, we’d be keen to hear from you.
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