The LAG3 (Lymphocyte activation gene 3, CD223) is a lymphocyte activation gene and a member of the Ig family. It is mainly expressed in activated T cells, NK cells, B cells and plasmacytoid DCs. LAG3 is a negative regulator of immunity and mainly binds to MHC class Ⅱ molecules to regulate the function of dendritic cells. The expression of LAG3 is associated with the negative immunoregulatory function of specific T cells. Inhibition of LAG3 function enhances the antitumor effect of specific CD8 + T cells, therefore LAG3 is a potential target for tumor immunotherapy.
Protein Expression Analysis
Splenocytes from both wild type (WT)C57BL/6 and B-hLAG3 homozygous mice were analyzed by flow cytometry. Mouse LAG3 + T cells were detectable in the WT mice, while human LAG3 + T cells were detectable in the B-hLAG3 homozygous mice. Mouse LAG3 + T cells were also detectable in the B-hLAG3 homozygous mice. The reason maybe that the anti-mouse LAG3 antibody cross-reacts with human LAG3.
Human LAG3 mAb efficacy evaluation (MC38)
Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hLAG3 mice. Mice were divided into control and treatment groups (n = 5) when the tumor volume was about 150±50 mm3. Anti-human LAG3 antibody Ab2, but not Ab1, significantly inhibited tumor growth in the homozygous B-hLAG3 mice, suggesting that B-hLAG3 mouse model is a powerful tool for human LAG3 antibody efficacy studies in vivo. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.
Combination therapy of LAG3 mAb (Relatimab Analog) and mPD-1 mAb
Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hLAG3 mice. Mice were divided into control and treatment groups (n=5) when the tumor size was approximately 150 ± 50 mm3. Combination of anti-hLAG3 antibody and anti-mPD-1 antibody significantly inhibited tumor growth in the homozygous B-hLAG3 mice, suggesting that B-hLAG3 mouse model is an effective tool for in vivo hLAG3 antibody efficacy evaluation study. The average ± SEM of tumor sizes are shown in the figure.
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