Human PBMC engraftment
Analysis of peripheral blood lymphocyte subpopulations. Human PBMCs (5E6) were intravenously implanted into homozygous B-NDG mice (female, 6 week-old, n=6). Blood from B-NDG mice was taken at different times after implantation of human PBMC for flow cytometric analysis. B-NDG mice showed a high percentage of human CD45+ cells, T cells. B-NDG mice exhibit reduced body weight and shortened survival likely due to GVHD effects caused by a high proportion of human immune cell reconstitution.
Bispecific antibody in vivo efficacy evaluation in B-NDG mice reconstituted with human PBMCs
B-NDG mice reconstituted with PBMCs cells were used for bispecific antibody efficacy studies Human B-luciferase-GFP Raji cells (5E5), PBMC (5E6) and antibody mixture were intravenously injected into B-NDG mice (n=4). (A) fluorescence imager was used to monitor tumor fluorescence in mice. (B) Body weight changes during treatment. Bispecific antibody shows significant inhibitory effects. The results indicate that establishing a CDX tumor model in B-NDG mice with reconstituted PBMCs provide a powerful preclinical model for in vivo evaluation of antibodies. Values are expressed as mean ± SEM.
B-NDG mice reconstituted with PBMCs were used for CD3×Claudin18.2 bispecific antibody efficacy studies. NUGC4 cells (5E6) were subcutaneously implanted after human PBMCs (5E6) were intravenously implanted into B-NDG mice (female, 7 week-old, n=6). The animals were grouped into control and treatment when the tumor size was approximately 50-80 mm3 and the percentage of human blood hCD45% were above 10%, at which time they were treated with drugs. (A) Anti human CD3×Claudin18.2 bispecific antibody (AMG 910 analog) inhibited NUGC4 tumor growth in human PBMC reconstituted B-NDG mice. (B) Body weight changes during treatment. CD3×Claudin18.2 bispecific antibody shows significant tumor inhibitory effects. The results indicate that establishing a CDX tumor model in B-NDG mice with reconstituted PBMCs provide a powerful preclinical model for in vivo evaluation of antibodies. Values are expressed as mean ± SEM.