|Strain Name||C57BL/6-Cd274tm1(CD274)Tnfrsf9tm1(TNFRSF9)/Bcgen||Common Name||B-hPD-L1/h4-1BB mice|
Cd274 (CD274 antigen)
TNFRSF9(tumor necrosis factor receptor superfamily, member 9)
Strain specific PD-L1 and 4-1BB expression analysis in homozygous B-hPD-L1/h4-1BB mice by flow cytometry.
Splenocytes were collected from WT and homozygous B-hPD-L1/h4-1BB (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific anti-PD-L1 and anti-4-1BB antibody. Mouse Pdl1 and 4-1BB were detectable in WT mice but not in homozygous B-hPD-L1/h4-1BB mice. Human PD-L1 and 4-1BB were exclusively detectable in homozygous B-hPD-L1/h4-1BB mice but not in WT mice.
Antitumor activity of anti-4-1BB antibody and anti-4-1BB-PD-L1 bispecific antibody in B-hPD-L1/h4-1BB mice.
(A) Anti-4-1BB antibody and anti-4-1BB-PD-L1 bispecific antibody inhibited B16F10-hPD-L1 tumor growth in B-hPD-L1/h4-1BB mice. B16F10-hPD-L1 cells were subcutaneously implanted into homozygous B-hPD-L1/h4-1BB mice (female, 7-week-old, n=6). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with anti-4-1BB antibody and bispecific antibody with doses and schedules indicated in panel. (B) Body weight changes during treatment. As shown in panel A, the bispecific antibody were more efficacious in controlling tumor growth in B-hPD-L1/h4-1BB mice compared with PBS and the anti-4-1BB antibody group, demonstrating that the B-hPD-L1/h4-1BB mice provide a powerful preclinical model for in vivo evaluation of anti-human PD-L1 antibody, anti-human 4-1BB antibody or related bispecific antibody. Values are expressed as mean ± SEM.