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靶点基(ji)因人(ren)源化小鼠(shu)

由于(yu)种属差(cha)异(yi),抗(kang)肿瘤药(yao)(yao)(yao)物作(zuo)用(yong)(yong)的(de)靶(ba)点(dian)(dian)分(fen)(fen)子可(ke)能(neng)在人(ren)(ren)(ren)和小(xiao)(xiao)实(shi)验(yan)(yan)动(dong)物之间不同,动(dong)物细(xi)胞(bao)上(shang)不存在此靶(ba)点(dian)(dian)或不能(neng)被(bei)药(yao)(yao)(yao)物识别,因(yin)而无(wu)法(fa)使(shi)用(yong)(yong)小(xiao)(xiao)型(xing)实(shi)验(yan)(yan)动(dong)物来(lai)进行非临床(chuang)研究评(ping)价。应用(yong)(yong)基(ji)(ji)(ji)因(yin)工(gong)程手段(duan)使(shi)小(xiao)(xiao)鼠表达人(ren)(ren)(ren)的(de)靶(ba)点(dian)(dian)分(fen)(fen)子基(ji)(ji)(ji)因(yin),称为靶(ba)点(dian)(dian)基(ji)(ji)(ji)因(yin)人(ren)(ren)(ren)源(yuan)化小(xiao)(xiao)鼠。免(mian)疫(yi)(yi)检(jian)查点(dian)(dian)(immune checkpoint)是近(jin)年来(lai)发现的(de)利用(yong)(yong)自身(shen)免(mian)疫(yi)(yi)功(gong)能(neng)抗(kang)肿瘤的(de)重(zhong)要药(yao)(yao)(yao)物靶(ba)点(dian)(dian)。针(zhen)对(dui)(dui)PD1/PDL1这一对(dui)(dui) “免(mian)疫(yi)(yi)刹车(che)”信号分(fen)(fen)子的(de)单抗(kang)药(yao)(yao)(yao)物已被(bei)证明具有(you)(you)强大的(de)抗(kang)肿瘤效用(yong)(yong)。由于(yu)这些抗(kang)体药(yao)(yao)(yao)物都是针(zhen)对(dui)(dui)人(ren)(ren)(ren)的(de)靶(ba)点(dian)(dian)设计和筛选(xuan),它可(ke)能(neng)只识别、结合(he)人(ren)(ren)(ren)的(de)PD1、PDL1,就无(wu)法(fa)用(yong)(yong)动(dong)物做(zuo)临床(chuang)前体内评(ping)估实(shi)验(yan)(yan)。为了解决这个问题,可(ke)以通过基(ji)(ji)(ji)因(yin)编辑技(ji)术将小(xiao)(xiao)鼠的(de)PD1、PDL1基(ji)(ji)(ji)因(yin)替换为人(ren)(ren)(ren)的(de)基(ji)(ji)(ji)因(yin),这样小(xiao)(xiao)鼠的(de)细(xi)胞(bao)上(shang)就表达人(ren)(ren)(ren)的(de) PD1、PDL1,可(ke)以用(yong)(yong)来(lai)试验(yan)(yan)抗(kang)人(ren)(ren)(ren)PD1、PDL1抗(kang)体药(yao)(yao)(yao)的(de)作(zuo)用(yong)(yong)。im体育公司已开发一系列免(mian)疫(yi)(yi)检(jian)查点(dian)(dian)分(fen)(fen)子的(de)基(ji)(ji)(ji)因(yin)人(ren)(ren)(ren)源(yuan)化小(xiao)(xiao)鼠,除PD-1、PDL-1外还(hai)有(you)(you)LAG3、TIM3、OX40、TIGIT等人(ren)(ren)(ren)源(yuan)化的(de)小(xiao)(xiao)鼠。另外还(hai)有(you)(you)应用(yong)(yong)于(yu)激活T细(xi)胞(bao)的(de)双(shuang)特异(yi)性抗(kang)体药(yao)(yao)(yao)评(ping)价的(de)CD3e人(ren)(ren)(ren)源(yuan)化小(xiao)(xiao)鼠。

 

靶点基(ji)因人源化小鼠(shu)包括(kuo)

 

hPD-1小(xiao)鼠(shu)

PD-1/mPDL-1null小鼠

PDL-1/mPDL-1null小鼠

hLAG3小鼠

hTIM3小鼠

hPD-1/hLAG3小鼠

hTGIT小鼠

hCD3e小鼠(shu)