hello,大家下午好��！最近北方總是寒風(fēng)陣陣，一瞅日歷，11月了！心情也隨之激動(dòng)起來(lái)了有木有？咳咳，小編在此溫馨提示大家，挑仔細(xì)點(diǎn)！誓要成為最美買(mǎi)家秀知道不！   

不過(guò)嘛，言歸正傳，今天的產(chǎn)品小鼠不過(guò)節(jié)（B-NDG已經(jīng)在促銷(xiāo)了，再打折小編真要吃土了啊~），不多說(shuō)，自產(chǎn)雙人源化B-hPD-1/hBTLA小鼠獻(xiàn)給大家~   

BTLA基因功能

    B細(xì)胞和T細(xì)胞衰減蛋白（B and T lymphocyte associated，BTLA）是另一種Ig超家族的檢查點(diǎn)負(fù)調(diào)分子，在結(jié)構(gòu)上和CTLA4及PD-1類(lèi)似，不僅表達(dá)于B細(xì)胞、T細(xì)胞、NK細(xì)胞，在樹(shù)突狀細(xì)胞和巨噬細(xì)胞中也有表達(dá)。BTLA與其配體HVEM（腫瘤壞死因子受體超家族成員）結(jié)合傳遞共抑制信號(hào)，在機(jī)體抗腫瘤免疫應(yīng)答中發(fā)揮負(fù)性調(diào)節(jié)作用，并與腫瘤的免疫逃逸機(jī)制相關(guān)。 BTLA抑制劑可以增強(qiáng)TCR信號(hào)通路，并恢復(fù)T細(xì)胞功能，成為腫瘤生物治療潛在的新靶點(diǎn)。

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, whereby 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 been 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 or agonism of inhibitory or stimulatory molecular pathways, respectively. 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 cells. The anti-PD1 and anti-PDL1 mAbs block the interaction of PD1 with PDL1, reversing the inhibitory signaling and promoting lymphocyte activation. Similarly, 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人源化小鼠

基本信息

打靶策略

B-hBTLA蛋白表達(dá)分析

圖2. B-hBTLA人源化小鼠脾細(xì)胞活化及流式檢測(cè)

結(jié)果顯示：在C57BL/6小鼠的B細(xì)胞中可檢測(cè)到mBTLA⁺細(xì)胞。在B-hBTLA純合鼠的B細(xì)胞中，可檢測(cè)到hBTLA⁺細(xì)胞。

抗人BTLA抗體藥效驗(yàn)證

圖3.利用B-hBTLA小鼠進(jìn)行抗人BTLA抗體藥效驗(yàn)證實(shí)驗(yàn)

將改造過(guò)的小鼠結(jié)腸癌MC38細(xì)胞（人源化HVEM并去除小鼠HVEM）移植到B-hBTLA純合小鼠體內(nèi)建立皮下腫瘤模型，待腫瘤體積約150±50mm3時(shí)將動(dòng)物入組至對(duì)照組和治療組(n=6)。

結(jié)果顯示：相同劑量下，不同抗人BTLA抗體展現(xiàn)對(duì)腫瘤的抑制效果不同；同一抗人BTLA抗體，不同劑量下也展現(xiàn)出不同抑瘤效果。A. 腫瘤平均體積±SEM，B. 小鼠平均體重±SEM。 結(jié)果證明： B-hBTLA小鼠是評(píng)估人BTLA抗體體內(nèi)藥效的有力工具。

百奧賽圖利用自主開(kāi)發(fā)的B-hPD-1/hBTLA 雙人源化小鼠，為研究該靶點(diǎn)抗體藥物的體內(nèi)藥效驗(yàn)證提供了有效的模型和有力的工具！

B-hPD-1/hBTLA 雙人源化小鼠

基本信息

打靶策略

B-hPD-1/hBTLA小鼠蛋白表達(dá)分析

圖4. B-hPD-1/hBTLA人源化小鼠脾細(xì)胞活化及流式檢測(cè)

結(jié)果顯示：在C57BL/6小鼠中可檢測(cè)到mPD-1⁺細(xì)胞。在B-hPD-1/hBTLA純合鼠中，可檢測(cè)到hPD-1+細(xì)胞。

圖5. B-hPD-1/hBTLA人源化小鼠脾細(xì)胞活化及流式檢測(cè)

結(jié)果顯示：在C57BL/6小鼠中可檢測(cè)到mBTLA⁺細(xì)胞。在B-hPD-1/hBTLA純合鼠中，可檢測(cè)到hBTLA⁺細(xì)胞。

   百奧賽圖盛產(chǎn)各類(lèi)基因打靶小鼠，免疫檢查點(diǎn)小鼠.....有意者歡迎隨時(shí)咨詢(xún)訂購(gòu)哦~

參考文獻(xiàn)

[1]Interfering with coinhibitory molecules: BTLA/HVEM as new targets to enhance anti-tumor immunity

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