Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia
Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia
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DOI：
10.1038/s41591-018-0146-z
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发表时间：
2018-10-01
期刊：
影响因子：
82.9
通讯作者：
Winckler, Wendy
中科院分区：
文献类型：
--
作者：
Orlando, Elena J.;Han, Xia;Winckler, Wendy
我们确定了嵌合抗原受体（CAR）治疗后CD 19（-）复发时CD 19的基因突变和杂合性丢失。这些突变存在于绝大多数耐药肿瘤细胞中，并且预计会导致具有无功能或不存在跨膜结构域的截短蛋白，从而导致表面抗原的丧失。这种CD 19的不可逆损失提倡替代靶向或组合CAR方法。
We identified genetic mutations in CD19 and loss of heterozygosity at the time of CD19(-) relapse to chimeric antigen receptor (CAR) therapy. The mutations are present in the vast majority of resistant tumor cells and are predicted to lead to a truncated protein with a nonfunctional or absent transmembrane domain and consequently to a loss of surface antigen. This irreversible loss of CD19 advocates for an alternative targeting or combination CAR approach.