Imaging CAR T cell therapy with PSMA-targeted positron emission tomography
Imaging CAR T cell therapy with PSMA-targeted positron emission tomography
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DOI：
10.1126/sciadv.aaw5096
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发表时间：
2019-07-01
期刊：
影响因子：
13.6
通讯作者：
Pomper, Martin G.
中科院分区：
文献类型：
--
作者：
Minn, Il;Huss, David J.;Pomper, Martin G.
嵌合抗原受体（CAR）T细胞治疗血液恶性肿瘤充满了几个未知数，包括参与靶肿瘤的功能性T细胞的数量，持久性和随后的扩展和收缩，以及毒性是否可以管理。使用报告转基因的CAR T细胞疗法的非侵入性连续成像可以定量地解决这些问题。我们已经用前列腺特异性膜抗原（PSMA）转导了抗CD 19 CAR T细胞，因为它是一种具有有限正常组织表达的人类蛋白质，并且具有正电子发射断层扫描（PET）和治疗性放射性配体的扩展阵列。我们证明，在急性淋巴细胞白血病的Nalm 6模型中，可以用[F-18]DCFPyL PET追踪⑶ 19-tPSMA（（N9 del））CART细胞。外周血和骨髓中的CD 19-tPSMA（（N9 del））CAR T细胞的数量与肿瘤中的那些之间的差异是明显的。这些发现强调了临床上对CAR T细胞分布进行非侵入性可重复监测的必要性。
Chimeric antigen receptor (CAR) T cell therapy for hematologic malignancies is fraught with several unknowns, including number of functional T cells that engage target tumor, durability and subsequent expansion and contraction of that engagement, and whether toxicity can be managed. Non-invasive, serial imaging of CAR T cell therapy using a reporter transgene can address those issues quantitatively. We have transduced anti-CD19 CAR T cells with the prostate-specific membrane antigen (PSMA) because it is a human protein with restricted normal tissue expression and has an expanding array of positron emission tomography (PET) and therapeutic radioligands. We demonstrate that CD19-tPSMA((N9del)) CART cells can be tracked with [F-18]DCFPyL PET in a Nalm6 model of acute lymphoblastic leukemia. Divergence between the number of CD19-tPSMA((N9del)) CAR T cells in peripheral blood and bone marrow and those in tumor was evident. These findings underscore the need for non-invasive repeatable monitoring of CAR T cell disposition clinically.