Please input keywords
*Verification code
*Verification Code
B-hPD-L1/h4-1BB mice
Strain Name C57BL/6-Cd274tm1(CD274)Tnfrsf9tm1(TNFRSF9)/Bcgen  Common Name  B-hPD-L1/h4-1BB mice
Background C57BL/6 Catalog number  120535
Related Genes 
Cd274 (CD274 antigen)
(tumor necrosis factor receptor superfamily, member 9)

Gene description

TNFRSF9 also called CD137 and 4-1BB, is a co-stimulatory molecule and is mainly expressed on the surface of T, B, NK and mononuclear cells. CD137 is activated by its ligand CD137L or activating anti-CD137 antibodies enhance tumor rejection because it is upregulated on T cells following activation and its engagement increases T cell proliferation and pro-inflammatory cytokine production. The clinical development of 4-1BB targeting therapy was slow due to the toxicity associated with overt immune activation.New therapeutic combinations with other immuno-modulatory and traditional anti-cancer treatments have revived excitement for the use of 4-1BB agonists in the clinical. PD-L1 (Programmed cell death ligand-1), also known as B7-H1 and CD274, is mainly expressed in antigen-presenting cells (APCs) and activated T cells. and highly expressed in a variety of solid tumors. PD-1 and PD-L1 interactions can reduce T Cell activation and promote tumor immune escape. The PD-1/PD-L1 signaling pathway can be blocked and antitumor immune response can be restored by using by anti-PD-1 or anti-PD-L1 antibodies to block the binding of PD1 to PD-L1
Biocytogen has developed a double humanized B-hPD-L1/h4-1BB mouse model to unlock the tremendous potential of combination therapy involving 4-1BB agonists and anti-PD-L1 antibodies.  

Protein expression analysis

from clipboard

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.

4-1BB-PD-L1 bispecific antibody Efficacy 

from clipboardAntitumor 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.