Hello, everyone, in the hot summer, there is no small series of product promotion, presumably you must not adapt. In recent years, immunization checkpoint drugs have become an important new drug in cancer treatment. Today, we introduce a humanized mouse for immunological checkpoints for babies, and at the same time, as a small- sized summer artifact, hOX40 mice. When Dangdang, then we will quickly enter the topic~
Introduction to OX40 gene function
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. The role of T cells, including cytokine production, proliferation, and survival of T cells, is further enhanced by the co-activation effect of the OX40/OX40L signal. OX40 antibody activator (Agonist) reduces intratumoral Tregs and increases antitumor activity.
Figure 1. OX40/OX40L interactions impact the four phases of the T cell lifespan [1]
The current published data show that a variety of OX40 antibody drugs have entered the clinical research stage, and more and more OX40 antibody drugs will enter the clinical stage, and the OX40 target drug research and development market will have great development potential. 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
Gene editing strategy
B-hOX40 protein expression analysis
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.
OX40 antibody efficacy validation: heterozygous mice
Figure 3. Anti-human OX40 antibody validation test using B-hOX40 mice   Â
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 mm 3 .
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     Â
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 the animals were enrolled into the control group and the treatment group (n=5) when the tumor volume was about 150 ± 50 mm 3 .
The results showed that anti-human OX40 antibody (MOXR0916 Analog) inhibited tumor growth. The results also 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
[1]. Jensen, SM, Maston, LD, Gough, MJ Signaling Through OX40 Enhances Antitumor Immunity [J]. Seminars in Oncology, 2010 Oct; 37 (5): 524-32.
[2].https://clinicaltrials.gov/ct2/results?cond=OX40&term=&cntry=&state=&city=&dist=
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