NFRSF9 (TNF receptor superfamily member 9), also called CD137 or 4-1BB, is mainly expressed on the surface of activated T, NK, and mononuclear cells. CD137 is activated by binding its ligand CD137L or an activated CD137 monoclonal antibody, which provides a co-stimulation signal for T cell activation and amplifies T cells and secreted cell factors. The co-stimulation signal mediated by it can multiply antigen presenting cells and result in the secretion of cell factors. Experiments show that CD137 co-stimulation can regulate the function of T cell and antigen presenting cells for antitumor immunity, providing new targets for tumor immunological therapies.
Targeting strategy ：
mRNA expression verification:
Fig 1. Molecular identification of B-h4-1BB humanized mice. m4-1BB mRNA expression was detected in spleen cells of B-h4-1BB heterozygous mice.
Protein expression verification:
Fig 2. B-h4-1BB humanized mice spleen cell activation and flow cytometry.
m4-1BB+ cells were detected in C57BL/6 mice. h4-1BB+ cells were detected in B-h4-1BB homozygous mice.
4-1BB antibody efficacy validation:
Fig 3. B-h4-1BB mice were used for h4-1BB antibody efficacy validation.Mouse colon cancer MC38 cells were subcutaneously transplanted into B-h4-1BB heterozygous mice, and animals were grouped into control to treatment groups (n=5), which include 2 antibodies and 2 doses, when the tumor size is approximately 100 mm3.Anti-h4-1BB antibody Ab2 shows substantially inhibitory effects at both doses, while Ab1 only inhibits tumor growth at the higher dose but not lower dose. The average±SEM of tumor sizes are shown in the figure.B-h4-1BB mice are effective tools for h4-1BB antibody efficacy validation.