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公司scidIL2rg公司原肌球蛋白1/BcgenHsd)由Biocytogen开发，现由Envigo授权，具有独特的高度免疫缺陷。下面，我们将讨论B-NraybetAPPDG模型的一些优点，并描述其可用性所带来的最新研究。
The features and benefits of the B-NDG model
B-NDG是一种白化的单基因敲除小鼠，通过删除普通γ链产生(IL2rg公司) 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，对人源性细胞的最小排斥使B-NDG小鼠成为PDXs（病人源性异种移植物）移植的理想宿主。该模型保留了肿瘤组织的异质性特征，准确地再现了患者的特征。
raybetAPPEnvigo的战略营销副总监Travis Rothrock告诉我们为什么他对这种研究模式的新可用性感到兴奋：“例如，B-NDG可以用于研究标准疗法，或者了解PDX将如何发展。但是，这种模型的真正好处是可以选择将其人源化，植入细胞系或PDX，让其生长，然后注射单克隆抗体或检查点抑制剂，看看它们是否能导致肿瘤随着时间的推移而缩小。”
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公司colorectal model+评估体内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.
+一种开发记忆性CAR-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小鼠来确定如何最佳地重新刺激细胞。这导致了生存率的提高和肿瘤发生的延迟。
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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