Strain Name: B6/JGpt-Pdcd1 em1Cin(hPDCD1) Lag3 emCin(hLAG3) /Gpt
Strain Type: Knock-in
Strain ID: T004621
1. Evaluation of efficacy and safety of human LAG3 inhibitors
2. Evaluation of the combined efficacy of human LAG3 inhibitor and human PD1 inhibitor
3. Anti-tumor Drug Research and Development
4. Research on autoimmune diseases
LAG3（Lymphocyte activation gene3）, a cell surface molecule expressed on activated T cells, NK cells, B cells and plasmacytoid dendritic cells. Studies have shown that knock out the LAG3 gene or in vivo antibodies blocking LAG3 function can increase the aggregation and effector function of antigen-specific CD8+ T cells in organs or tumors, Therefore, blocking LAG3 is a potential tumor treatment. B6-hPD1/hLAG3 mice is ideal animal model to evaluate the efficacy of human LAG3 antibody, human PD1 antibody and their combo treatment.
Detection of PD1 and LAG3 expression
B6-hPD1/hLAG3 homozygous mice expressed human PD1 on T cell surface.
B6-hPD1/hLAG3 homozygous mice expressed human LAG3 on T cell surface.
The T/B/NK cell ratio detection
Fig.5 Detection the T/B/NK cell ratio in B6-hPD1/hLAG3 mice. B6-hPD1/LAG3 homozygous, heterozygous and wild type mice have the same T/B/NK cell ratio.
Anti-tumor Efficacy Test
Evaluation of in vivo efficacy of Anti-hLAG3 and Anti-hPD1 by subcutaneous inoculation of MC38 model in B6-hPD1/hLAG3 mice
Fig.6 In vivo efficacy test based on B6-hPD1/hLAG3.
Murine colon cancer MC38 cells was cultured to logarithmic growth phase and inoculated subcutaneously into 6-8 weeks old B6-hPD1/hLAG3 mice. Mice were divided into Vehicle groups, Anti-hPD1 groups, Anti-hPD1 + Anti-hLAG3 groups when the tumor size was about 120 mm3, and were treated with the appropriate medication. Administer twice a week for a total of 4 times.
Result Anti-hPD1 group inhibit tumor growth (TGI = 71.88%), Anti-hPD1 + Anti-hLAG3 group inhibit tumor growth (TGI = 76.03%)(Fig.6A).The trend of weight change in mice is consistent（Fig.6B）.
Indicating B6-hPD1/hLAG3 mice are powerful tools to evaluate the combined efficacy of anti-hPD1 and anti-hLAG3 antibodies in vivo.
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