hPD-1
Nomenclature
C57BL/6Smoc-Pdcd1em1(hPDCD1) /Smoc
Cat. NO.
NM-HU-00015
Strain State
Repository Live
Gene Summary
Gene Symbol
Pdcd1
Model Description
The endogenous mouse Pdcd1 gene was replaced by human PDCD1(PD-1) gene .
Validation Data
Data from flow cytometry (FACS) analysis
Fig1 . Expression of PD-1 in the activated spleen lymphocytes of humanized PD-1 Homozygous mice is detected by FACS.
In vivo validation in a MC38 tumor-bearing model of humanized PD-1 mice
Fig2 . In vivo anti-tumor effect of an anti-human PD-1 antibody in a humanized mouse model of PD-1. Anti-human-PD-1 drugs significantly inhibited the growth of MC38 tumors in PD-1 mice, demonstrating that the humanized PD-1 mice can be used to assess the anti-human PD-1 antibody.
A. Mean volume ± SEM of tumor tissues (completed in cooperation with Genscript).
In vivo validation of anti-tumor efficacy in a MC38 tumor-bearing model of humanized PD-1 mice. Homozygous humanized PD-1 mice were inoculated with MC38 colon cancer cells. After the tumors grew to 100 mm3, the animals were randomly assigned into a control group and a treatment group (n=8). The drug was given twice a week for a total of 4 administrations. The results showed that Keytruda, a drug targeting human PD-1, exerted a very significant anti-tumor effect (p<0.001), demonstrating that the humanized PD-1 mice are a good in vivo model for validating the efficacy of antibodies targeting human PD-1.
B. Mean volume ± SEM of tumor tissues. C. Mean body weight ± SEM of mice (data were obtained in cooperation with PharmaLegacy).
In vivo dose validation of anti-tumor efficacy in a MC38 tumor-bearing model of humanized PD-1 mice. Homozygous humanized PD-1 mice were inoculated with MC38 colon cancer cells. After the tumors grew to about 90 mm3, the animals were randomly assigned into a control group and a treatment group (n=9). The results showed that the antibodies targeting human PD-1 showed a very significant antitumor effect (p<0.001), and such antitumor effect is dose-dependent.
Fig3 . In vivo dose validation in a MC38 tumor-bearing model of humanized PD-1 mice. Homozygous humanized PD-1 mice were inoculated with MC38 colon cancer cells. After the tumors grew to 100 mm3, the animals were randomly assigned into a control group and a treatment group (n=8). The drug was given twice a week for a total of 4 administrations.
Case Study
As one of the first five anti-PD-1 drugs with BLAs accepted by CFDA, Sintilimab has shown potent T cell stimulating activity and significant anti-tumor efficacy. (read more)
Fig4 . In vivo hPD-1 knock-in mouse model to test anti-tumor efficacy of Sintilimab. (A) Tumor growth inhibition (TGI) of MC38 tumors in hPD-1 knock-in mice of individual animals treated with different doses of Sintilimab. (B) Effect of Sintilimab on percentage changes in mouse body weight(mean). (C) Changes in ratios of tumor infiltrating CD4+, CD8+ and Treg cells. For d8: IgG (n = 2); Sintilimab (n = 2). For d14, n = 3 for all groups. P values were calculated using a two-tailed t-test method.
Publications
Enhanced Therapeutic Efficacy of a Novel Oncolytic Herpes Simplex Virus Type 2 Encoding an Antibody Against Programmed Cell Death 1
References:Molecular Therapy Oncolytics
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