Hello, good afternoon everyone! Recently, the north is always in the cold, a calendar, November! The mood is also excited, is there a wood? Keke, Xiaobian here to remind everyone, pick carefully! Vow to be the most beautiful buyer show knows no!
However, it is a good news, today's product mice are not out of date (B-NDG is already in promotion, and then discounted Xiaobian really want to eat soil ~), not much to say, self-produced double source B-hPD-1/hBTLA The mouse is dedicated to everyone~
BTLA gene function
B and T lymphocyte associated (BTLA) is another checkpoint negative tone molecule of the Ig superfamily. It is structurally similar to CTLA4 and PD-1, not only expressed in B cells, T cells, NK cells are also expressed in dendritic cells and macrophages. BTLA binds to its ligand HVEM (a member of the tumor necrosis factor receptor superfamily) to transmit a co-suppressive signal, which plays a negative regulatory role in the body's anti-tumor immune response and is associated with the immune escape mechanism of the tumor. BTLA inhibitors can enhance the TCR signaling pathway and restore T cell function, making it a potential new target for tumor biotherapy.
Fig.1. (A) Interactions around PD1 and HVEM. PD1 belongs to the B7/CD28 (Immunoglobulin) superfamily and delivers negative signals upon binding to its ligands, PD-L1 and PD-L2. Recently, an unexpected interaction has been shown Between PDL1 and CD80, where CD80 expressed on T cells can potentially behave as a receptor by delivering inhibitory signals when engaged by PDL1. CD80 and CD86 bind to the same two receptors, the stimulatory CD28 and the inhibitory CTL-associated-antigen-4 ( CTLA-4) molecules. HVEM from the TNF/TNFR superfamily is clearly now a central immune molecule given the complexity of its interactions. HVEM has initially discovered as the coreceptor for the glycoprotein D (gD) of the herpes simplex virus 1 (HSV -1), allowing the entry of the virus in the cell. HVEM interacts with LIGHT and lymphotoxin 3 to stimulate T cell responses. More recently, two novel ligands inhibiting T cell responses have been identified for HVEM: BTLA and CD160, a glycosphingolipid- Linked Protein, both belonging to the Ig superfamily, highlighting a crosstalk between the TNF-TNFR superfamily and the Ig superfamily. (B) Targeting coinhibitory molecules with monoclonal antibodies. Monoclonal antibodies (mAbs) are the primary immunotherapeutic modality used to promote immune function via antagonism Cancer cells exploit the upregulation of coinhibitory molecules to inhibit T cell activation and to evade antitumor immunity. Indeed, PD1 is upregulated in TILs from many tumors and its ligands PDL1 and PDL2 are overexpressed in cancer The anti-PD1 and anti-PDL1 mAbs block the interaction of PD1 with PDL1, reversing the inhibitory signaling and promoting lymphocyte activation. similar, high expression of BTLA was reported in tumor antigen-specific T cells from melanoma, thus BTLA would mediate Inhibition of lymphocyte activation through engagement with its ligand HVEM expressed on tumors [1] .
hBTLA humanized mouse
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B-hBTLA protein expression analysis
Figure 2. Activation and flow cytometry of B-hBTLA humanized mouse spleen cells
The results showed that mBTLA + cells were detectable in B cells of C57BL/6 mice. hBTLA + cells were detected in B cells of B-hBTLA homozygous mice.
Anti-human BTLA antibody validation
Figure 3. Anti-human BTLA antibody validation test using B-hBTLA mice
The modified mouse colon cancer MC38 cells (humanized HVEM and mouse HVEM) were transplanted into B-hBTLA homozygous mice to establish a subcutaneous tumor model. Animals were enrolled into control at a tumor volume of approximately 150±50 mm3. Group and treatment group (n=6).
The results showed that different anti-human BTLA antibodies showed different inhibitory effects on tumors at the same dose; the same anti-human BTLA antibody also showed different anti-tumor effects at different doses. A. Mean tumor volume ± SEM, B. Mouse mean body weight ± SEM. The results demonstrate that B-hBTLA mice are a powerful tool for assessing the in vivo efficacy of human BTLA antibodies.
Bio-Stuart uses the self-developed B-hPD-1/hBTLA double-sourced mouse to provide an effective model and powerful tool for studying the in vivo efficacy of the target antibody drug!
B-hPD-1/hBTLA double-sourced mice
Basic Information
Shooting strategy
Protein expression analysis of B-hPD-1/hBTLA mice
Figure 4. Activation and flow cytometry of B-hPD-1/hBTLA humanized mouse spleen cells
The results showed that mPD-1 + cells were detectable in C57BL/6 mice. In B-hPD-1/hBTLA homozygous mice, hPD-1+ cells were detected.
Figure 5. Activation and flow cytometry of spleen cells from B-hPD-1/hBTLA humanized mice
The results showed that mBTLA + cells were detectable in C57BL/6 mice. In B-hPD-1/hBTLA homozygous mice, hBTLA + cells were detected.
Baiao Sai Tu is rich in all kinds of gene targeting mice, immune checkpoint mice..... Interested parties are welcome to consult and order at any time~
references
[1]Interfering with coinhibitory molecules: BTLA/HVEM as new targets to enhance anti-tumor immunity
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