The Human Immune System Reconstituted B-NDG Mouse Models are Perfect Tools for CAR-T and Therapeutic Antibody Preclinical Efficacy Evaluation
Author: Qingcong Lin, Yanan Guo, Yuelei Shen
The B-NDG mice (NOD-Prkdcscid Il2rgtm1/Bcgen) were independently developed by Biocytogen to knockout IL2rg gene in NOD-SCID mouse background. Here we demonstrated that B-NDG, as one of the most severe immunodeficient mice, completely lack of mature T, B, and NK cells, and were deficient in cytokine signaling.
We provided evidence that the B-NDG mice inoculated with human tumor cells can be used for CAR-T therapy evaluation. In addition, the B-NDG mice are one of the best models for human immune system reconstitution using either PBMC or CD34+ hematopoietic stem cells. In order to reduce the GvHD, we have generated B-NDG B2M mice, on which B2M gene was knocked-out. B-NDG B2M mice have longer therapeutic window as compared with B-NDG mice for PBMC reconstitution and have been successfully used for antibody efficacy studies.
Other than PBMCs, human CD34+ hematopoietic stem cells have been successfully grafted in B-NDG mice, in which all major human myeloid and lymphoid lineage cell types were fully developed, reconstituting a functional human immune system. Using B-NDG mice, we have successfully established more than 300 PDX models and 200 CDX models. In conclusion, we have developed more powerful and predictive mouse models for preclinical pharmacology evaluation of CAR-T and therapeutic antibodies.