Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell
通过转导单个白血病B细胞诱导对嵌合抗原受体T细胞疗法的耐药性
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作者:Marco Ruella # ,Jun Xu # ,David M Barrett # ,Joseph A Fraietta ,Tyler J Reich ,David E Ambrose ,Michael Klichinsky ,Olga Shestova ,Prachi R Patel ,Irina Kulikovskaya ,Farzana Nazimuddin ,Vijay G Bhoj ,Elena J Orlando ,Terry J Fry ,Hans Bitter ,Shannon L Maude ,Bruce L Levine ,Christopher L Nobles ,Frederic D Bushman ,Regina M Young ,John Scholler ,Saar I Gill ,Carl H June ,Stephan A Grupp ,Simon F Lacey ,J Joseph Melenhorst
| 期刊: | Nature Medicine | 影响因子: | 58.700 |
| 时间: | 2018 | 起止号: | 2018 Oct;24(10):1499-1503. |
| doi: | 10.1038/s41591-018-0201-9 | 种属: | Goat |
| 方法学: | ELISA、Most、WB | 靶点: | IgG Fc |
| 研究方向: | 信号转导、免疫、细胞生物学、肿瘤 | 疾病类型: | 白血病 |
| 细胞类型: | B细胞、T细胞 | 信号通路: | T Cell Receptor |
Abstract
We report a patient relapsing 9 months after CD19-targeted CAR T cell (CTL019) infusion with CD19- leukemia that aberrantly expressed the anti-CD19 CAR. The CAR gene was unintentionally introduced into a single leukemic B cell during T cell manufacturing, and its product bound in cis to the CD19 epitope on the surface of leukemic cells, masking it from recognition by and conferring resistance to CTL019.
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