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靶(ba)点基因(yin)人源化小(xiao)鼠

由(you)于(yu)(yu)种属(shu)差异,抗(kang)(kang)(kang)肿(zhong)瘤(liu)(liu)药(yao)(yao)物(wu)(wu)(wu)(wu)作(zuo)用(yong)(yong)(yong)(yong)的(de)(de)(de)(de)靶(ba)(ba)点(dian)(dian)(dian)分(fen)子(zi)可(ke)能(neng)在(zai)人(ren)和(he)小实验动物(wu)(wu)(wu)(wu)之(zhi)间不(bu)同(tong),动物(wu)(wu)(wu)(wu)细(xi)胞(bao)上不(bu)存在(zai)此(ci)靶(ba)(ba)点(dian)(dian)(dian)或(huo)不(bu)能(neng)被药(yao)(yao)物(wu)(wu)(wu)(wu)识(shi)别(bie)(bie),因(yin)(yin)而无(wu)法(fa)使(shi)(shi)用(yong)(yong)(yong)(yong)小实验动物(wu)(wu)(wu)(wu)来进行非临(lin)床研(yan)究评价。应(ying)用(yong)(yong)(yong)(yong)基因(yin)(yin)工程手(shou)段使(shi)(shi)小鼠(shu)表达(da)人(ren)的(de)(de)(de)(de)靶(ba)(ba)点(dian)(dian)(dian)分(fen)子(zi)基因(yin)(yin),称为靶(ba)(ba)点(dian)(dian)(dian)基因(yin)(yin)人(ren)源化小鼠(shu)。免(mian)疫(yi)检(jian)查点(dian)(dian)(dian)(immune checkpoint)是(shi)近(jin)年(nian)来发现的(de)(de)(de)(de)利用(yong)(yong)(yong)(yong)自身免(mian)疫(yi)功能(neng)抗(kang)(kang)(kang)肿(zhong)瘤(liu)(liu)的(de)(de)(de)(de)重要药(yao)(yao)物(wu)(wu)(wu)(wu)靶(ba)(ba)点(dian)(dian)(dian)。针对PD1/PDL1这(zhei)一对 “免(mian)疫(yi)刹车(che)”信号分(fen)子(zi)的(de)(de)(de)(de)单抗(kang)(kang)(kang)药(yao)(yao)物(wu)(wu)(wu)(wu)已(yi)被证明具有强大的(de)(de)(de)(de)抗(kang)(kang)(kang)肿(zhong)瘤(liu)(liu)效用(yong)(yong)(yong)(yong)。由(you)于(yu)(yu)这(zhei)些抗(kang)(kang)(kang)体药(yao)(yao)物(wu)(wu)(wu)(wu)都是(shi)针对人(ren)的(de)(de)(de)(de)靶(ba)(ba)点(dian)(dian)(dian)设计的(de)(de)(de)(de)筛选(xuan)的(de)(de)(de)(de),它可(ke)能(neng)只识(shi)别(bie)(bie)、结合人(ren)的(de)(de)(de)(de)PD1、PDL1,就无(wu)法(fa)用(yong)(yong)(yong)(yong)动物(wu)(wu)(wu)(wu)做(zuo)临(lin)床前体内评估实验。为了解决这(zhei)个问题,可(ke)以通过基因(yin)(yin)编辑技(ji)术将(jiang)小鼠(shu)的(de)(de)(de)(de)PD1、PDL1基因(yin)(yin)替(ti)换为人(ren)的(de)(de)(de)(de)基因(yin)(yin),这(zhei)样小鼠(shu)的(de)(de)(de)(de)细(xi)胞(bao)上就表达(da)人(ren)的(de)(de)(de)(de) PD1、PDL1,可(ke)以用(yong)(yong)(yong)(yong)来试验抗(kang)(kang)(kang)人(ren)PD1、PDL1抗(kang)(kang)(kang)体药(yao)(yao)的(de)(de)(de)(de)作(zuo)用(yong)(yong)(yong)(yong)。im体育公司(si)已(yi)开发一系列免(mian)疫(yi)检(jian)查点(dian)(dian)(dian)分(fen)子(zi)的(de)(de)(de)(de)基因(yin)(yin)人(ren)源化小鼠(shu),除PD-1、PDL-1外还有LAG3、TIM3、OX40、TIGIT等(deng)人(ren)源化的(de)(de)(de)(de)小鼠(shu)。另外还有应(ying)用(yong)(yong)(yong)(yong)于(yu)(yu)激(ji)活T细(xi)胞(bao)的(de)(de)(de)(de)双特异性抗(kang)(kang)(kang)体药(yao)(yao)评价的(de)(de)(de)(de)CD3e人(ren)源化小鼠(shu)。

 

靶点基因人(ren)源化小(xiao)鼠包括

 

hPD-1小鼠

hPD-1/mPDL-1null小鼠

hPDL-1/mPDL-1null小鼠(shu)

hLAG3小鼠

hTIM3小(xiao)鼠

hPD-1/hLAG3小鼠

hTGIT小鼠

hCD3e小鼠