The brilliant star of the target of immune activator - OX40 target
New Year's first sword - OX40 target
The new year, the new weather, here is a small year for everyone to worship a good year! I believe that all the babies are familiar with some drugs related to tumor immunotherapy. Many drugs have been marketed and used for treatment. It is always a hot spot for immunology research to develop more drugs that can improve the immune system's ability to recognize and kill tumors. one. So, today's Xiaobian is to bring you the brilliant star of the immune activator target area - OX40 target .
Gene background
OX40, also known as Tnfrsf4 (Tumor necrosis factor receptor superfamily, member 4), is mainly expressed on the surface of activated CD4 + and CD8 + T cells , and binding to OX40 ligand can stimulate the activation of CD8 + T cells. Through the co-activation effect of the OX40/OX40L signal, the functions of T cells, including the production and proliferation of cytokines and the survival of T cells, are further enhanced. OX40 antibody activator (Agonist) reduces intratumoral Tregs and increases antitumor activity.
Figure 1. OX40 promotes T cell proliferation [1]
Currently published data show that there are a variety of OX40 antibody drugs have been in clinical studies, follow-up more and more of OX40 antibody drug will enter clinical phase, OX40 targets for drug development market has great potential for development, final For the benefit of human medicine.
Some progress is shown in the table below:
Table 1. Clinical source information of OX40 antibody drugs [2]
The B-hTNFRSF4 (OX40) humanized mouse developed by Biotase provides a powerful tool for scientists to validate the validation of this target antibody drug.
Basic Information
Targeting of policy
Protein expression
Figure 2. Activation and flow cytometry of B-hOX40 humanized mouse spleen cells
The results showed that mOX40 + cells were detectable in C57BL/6 mice. In B-hOX40 homozygous mice, hOX40 + cells were detected.
Model validation
OX40 antibody efficacy validation: heterozygous mice
Figure 3. Anti-human OX40 antibody validation test using B-hOX40 mice
Mouse colon cancer cell line MC38 was transplanted subcutaneously into B-hOX40 hybrid mice, and the animals were enrolled into the control group and the treatment group (n=5) when the tumor volume was about 100 mm3.
The results showed that the TGI of the three dose groups was about 50%, and the efficacy of the 0.1 mg/kg group was decreased at the end of the experiment. The 1 mg/kg and 10 mg/kg groups were statistically different from the control. p<0.05). Administration has a significant inhibitory effect on tumor growth. A. Mean tumor volume ± SEM, B. Mouse mean body weight ± SEM.
The results demonstrate that B-hOX40 mice are a powerful tool for assessing the in vivo efficacy of human OX40 antibodies.
OX40 antibody efficacy validation: homozygous mouse
Figure 4. Anti-human OX40 antibody validation test using B-hOX40 mice
Mouse colon cancer cell line MC38 was transplanted subcutaneously into B-hOX40 homozygous mice, and animals were enrolled into control group and treatment group (n=5) when the tumor volume was about 100 mm3.
The results showed that anti-human OX40 antibody has an inhibitory effect on tumor growth. A. Mean tumor volume ± SEM, B. Mouse mean body weight ± SEM.
The results demonstrate that B-hOX40 mice are a powerful tool for assessing the in vivo efficacy of human OX40 antibodies.
Validation of human OX40 antibody (MOXR0916 Analog)
Figure 5. Efficacy validation of anti-human OX40 antibody (MOXR0916 Analog) using B-hOX40 mice
Mouse colon cancer cell line MC38 was transplanted subcutaneously into B-hOX40 homozygous mice, and animals were enrolled into control group and treatment group (n=5) when the tumor volume was about 150±50 mm3.
The results showed that anti-human OX40 antibody (MOXR0916 Analog) inhibited tumor growth. A. Mean tumor volume ± SEM, B. Mouse mean body weight ± SEM.
The results demonstrate that B-hOX40 mice are a powerful tool for assessing the in vivo efficacy of human OX40 antibodies.
Nowadays, the rapid development of the bio-pharmaceutical industry has spurred the enthusiasm of major pharmaceutical companies to develop new antibody drugs. The Bio-Sai charts are rich in all kinds of gene-targeting mice. Welcome to contact us.
Reference material resources
1.http://
2.https://clinicaltrials.gov/ct2/results?cond=OX40&term=&cntry=&state=&city=&dist=
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