Imaging of Sleeping Beauty-Modified CD19-Specific T Cells Expressing HSV1-Thymidine Kinase by Positron Emission Tomography.
Imaging of Sleeping Beauty-Modified CD19-Specific T Cells Expressing HSV1-Thymidine Kinase by Positron Emission Tomography.
复制标题
通过正电子发射断层扫描对表达 HSV1-胸苷激酶的睡美人修饰 CD19 特异性 T 细胞进行成像。
DOI：
10.1007/s11307-016-0971-8
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发表时间：
2016
影响因子：
3.1
通讯作者：
C
中科院分区：
文献类型：
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作者：
Najjar,AmerM;Manuri,PallaviR;Olivares,Simon;Flores2nd,Leo;Mi,Tiejuan;Huls,Helen;Shpall,ElizabethJ;Champlin,RichardE;Turkman,Nashaat;Paolillo,Vincenzo;Roszik,Jason;Rabinovich,Brian;Lee,DeanA;Alauddin,Mian;Gelovani,Juri;C
目的我们已经在表达CD19特异性嵌合抗原受体(CAR)的T细胞中引入了正电子发射断层扫描(PET)功能，以非侵入性地监测过继转移的细胞。结果培养4周后，90%的培养细胞对CD19+靶细胞有特异性杀伤作用，可被更昔洛韦消融，并可通过生物发光成像和注射2′-deoxy-2′-[18F]fluoro-5-ethyl-1-β-d-arabinofuranosyl-uracil后的正电子发射体层析([18F]FEAU)在体内检测到。
PurposeWe have incorporated a positron emission tomography (PET) functionality in T cells expressing a CD19-specific chimeric antigen receptor (CAR) to non-invasively monitor the adoptively transferred cells.ProceduresWe engineered T cells to express CD19-specific CAR, firefly luciferase (ffLuc), and herpes simplex virus type-1 thymidine kinase (TK) using the non-viral-basedSleeping Beauty(SB) transposon/transposase system adapted for human application. Electroporated primary T cells were propagated on CD19+artificial antigen-presenting cells.ResultsAfter 4 weeks, 90 % of cultured cells exhibited specific killing of CD19+targetsin vitro, could be ablated by ganciclovir, and were detectedin vivoby bioluminescent imaging and PET following injection of 2′-deoxy-2′-[18F]fluoro-5-ethyl-1-β-d-arabinofuranosyl-uracil ([18F]FEAU).ConclusionThis is the first report demonstrating the use of SB transposition to generate T cells which may be detected using PET laying the foundation for imaging the distribution and trafficking of T cells in patients treated for B cell malignancies.