OX40 gene function
OX40 (Tumor necrosis factor receptor superfamily, member 4, also known as Tnfrsf4 ), is mainly expressed on the surface of activated CD4+ and CD8+ T cells, and its binding with the OX40L ligand can stimulate CD8+ T cell activation. Through the coactivation effect of OX40/OX40L signaling, the function of T cells, including cytokine production, proliferation and T cell survival, is further enhanced. An OX40 antibody agonist (Agonist) can reduce Regulatory T cells (Tregs) and improve anti-tumor activity.
mRNA expression verification
Fig 1. Molecular identification of B-hOX40 humanized mice. mOX40 mRNA expression was detected in spleen cells of B-hOX40 heterozygous mice.
Protein expression verification
Fig 2. B-hOX40 humanized mice spleen cell activation and flow cytometry.
mOX40+ cells were detected in C57BL/6 mice. hOX40+ cells were detected in B-hOX40 homozygous mice.
OX40 antibody pharmacological verification
Fig 3. B-hOX40 mice were used in OX40 antibody efficacy experiments. Mouse colon cancer cells (MC38) were subcutaneously transplanted into B-hOX40 heterozygous mouse. Control and experimental animal groups (n=5) were treated when the tumor volume was about 100mm3.
Tumor growth inhibition (TGI) of the 3 dose groups was about 50%, and the efficacy of the 0.1 mg/kg group at the final time point was decreased. Compared to the control group, the 1 mg/kg and 10 mg/kg group was statistically different (p<0.05). The dosing clearly shows suppression function for tumor growth. Average tumor volume ±SEM is indicated in the figure. This result demonstrates that the B-hOX40 mouse is an effective in vivo efficacy tool for the human OX40 antibody.