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

Strain specific LAG3 expression analysis in homozygous B-hLAG3 mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hLAG3 (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific anti-LAG3 antibody. Mouse LAG3 was detectable in WT and homozygous B-hLAG3 mice due to the anti-mouse LAG3 antibody cross-reacts with human LAG3. Human LAG3 was exclusively detectable in homozygous B-hLAG3 but not WT mice.

Antitumor activity of anti-human LAG3 antibodies in B-hLAG3 mice. (A) Anti-human LAG3 antibodies inhibited MC38 tumor growth in B-hLAG3 mice. Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hLAG3 mice (female, 6-7 week-old, n=5). Mice were grouped when tumor volume reached approximately 100 mm³, at which time they were treated with two anti-human LAG3 antibodies with doses and schedules indicated in panel (B) Body weight changes during treatment. As shown in panel A, anti-human LAG3 antibodies were efficacious in controlling tumor growth in B-hLAG3 mice, demonstrating that the B-hLAG3 mice provide a powerful preclinical model for in vivo evaluation of anti-human LAG3 antibodies. Values are expressed as mean ± SEM.