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Tumor model & pharmacological efficacy trial

2017-05-25 16:10:25.0

The B-NDG mice(NOD-Prkdcscid Il2rgtm1/Bcgen)were independently developed by Biocytogen. These mice, which are on a NOD-scid genetic background and have the IL2rg gene knocked out, are internationally recognized as having the highest degree of immuno-deficiency, and serve as the best model for human cell or tissue transplantation.


CDX lymph cancer metastasis model in B-NDG mouse


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Fig 1. Successful engraftment of Raji cells in B-NDG mice.

The same amount (5x106) of Raji cells were injected into B-NDG, NOD-scid and BALB/c Nude mice. We recorded and analyzed the following parameters in the mice at different time points: (A) The living situation of mice after cell inoculation, and constructed Kaplan-Merier survival curves. (B) Measured the body weight (g) change each week after inoculation, and calculated weights relative to weights the day animals were inoculated. (C) Measured the percentage change of human cells in mouse peripheral blood. After inoculation of Raji cells, we took 100 μl of whole blood via retro-orbital venous plexus each week, extracted DNA, and determined the ratio of human cells in peripheral blood of mice by q-PCR. (D) Compared livers of mice after Raji cell inoculation. After the weight of the mice was reduced by more than 20% after inoculation, we euthanized the mice, dissected the viscera, and took pictures. (E) Immunohistochemical staining of mice viscera after Raji cell inoculation. After the weight of the mice was reduced by more than 20% after inoculation, we embedded mouse livers and spleens into wax for immunohistochemical assays. The primary antibody is murine anti-human mitochondrial membrane protein antibody (Millipore, MAB1273), and the magnification is 400x.


Drug efficacy study


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Fig 3. We reconstructed the immune system of B-NDG mice with human CD34+ cells and i.v. injected 5x105 Raji-Fluc cells to test the effect of human PD-1 antibody on tumor growth. 5 days after Raji-Fluc cells were injected, the humanized PD-1 antibody was injected, and a dramatic inhibitory effect on tumor cells was observed.

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