The B-NDG mice (NOD-Prkdcscid Il2rgtm1/Bcgen), independently developed by Biocytogen, display a severe immunodeficiency phenotype, with no mature T, B or functional NK cells, and deficient in cytokine signaling. The B-NDG mouse is one of the best models for reconstitution of human immune system using peripheral blood mononuclear cells (PBMC) or hematopoietic stem cells (CD34+). Human PBMC reconstituted well in B-NDG mice, with the percentage of hCD45+ cells was over 50% in five weeks. To further analyze the subsets of immune cell composition, we found the majority of human cells were CD8+ T lymphocytes. Other than PBMC, human CD34+ hematopoietic stem cells also demonstrated a high-engraftment efficacy in B-NDG mice. Successful engraftment of CD34+ cells develops all major cell types via myeloid and lymphoid lineage to reconstitute functional human immune system. At 10 weeks post CD34+ cell implantation, the percentage of hCD45+ cells is over 30% with detectable human T, B and NK cells. Therefore, the immuno-humanized B-NDG mice are useful tools for studying hematopoiesis, immunology, infectious disease, and ES/iPS cell research. With barely any rejection to human derived cells, the B-NDG mouse is an ideal host for transplantation of PDX (Patient-Derived Xenograft), and retains the high heterogeneity characteristics of tumor tissues. Each PDX model can be considered as a single tumor patient and fully embodies the patient group characteristics. We have a collection of various PDX models including leukemia, breast cancer, gastric, lung, pancreatic, and colon et al. The humanized PDX model by implantation of PDX on the immuno-humanized B-NDG mice will be a promising tool to evaluate the in vivo efficacy of immune checkpoint antibodies in monotherapy or in combination. Therefore, therapeutic efficacy studies using B-NDG based PDX models are more meaningful and predictive in preclinical drug development and discovery.
Citation Format: Meiling Zhang, Chaoshe Guo, Yuelei Shen, Yanan Guo. The B-NDG mouse is a perfect tool for immune system humanization and patient derived xenograft transplantation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1157.