复发性胶质瘤靶向T细胞免疫治疗的报告基因成像
Reporter gene imaging of targeted T cell immunotherapy in recurrent glioma.
作者信息
Keu Khun Visith, Witney Timothy H, Yaghoubi Shahriar, Rosenberg Jarrett, Kurien Anita, Magnusson Rachel, Williams John, Habte Frezghi, Wagner Jamie R, Forman Stephen, Brown Christine, Allen-Auerbach Martin, Czernin Johannes, Tang Winson, Jensen Michael C, Badie Behnam, Gambhir Sanjiv S
机构信息
Department of Radiology, Molecular Imaging Program, Stanford University, Palo Alto, CA, 94305, United States.
Division of Nuclear Medicine, Hôpital de la Cité-de-la-Santé de Laval, QC, H7M 3L9, Canada.
出版信息
Sci Transl Med. 2017 Jan 18;9(373). doi: 10.1126/scitranslmed.aag2196.
High-grade gliomas are aggressive cancers that often become rapidly fatal. Immunotherapy using CD8 cytotoxic T lymphocytes (CTLs), engineered to express both herpes simplex virus type 1 thymidine kinase (HSV1-TK) and interleukin-13 (IL-13) zetakine chimeric antigen receptor (CAR), is a treatment strategy with considerable potential. To optimize this and related immunotherapies, it would be helpful to monitor CTL viability and trafficking to glioma cells. We show that noninvasive positron emission tomography (PET) imaging with 9-[4-[F]fluoro-3-(hydroxymethyl)butyl]guanine ([F]FHBG) can track HSV1-tk reporter gene expression present in CAR-engineered CTLs. [F]FHBG imaging was safe and enabled the longitudinal imaging of T cells stably transfected with a PET reporter gene in patients. Further optimization of this imaging approach for monitoring in vivo cell trafficking should greatly benefit various cell-based therapies for cancer.
高级别胶质瘤是侵袭性癌症，通常会迅速致命。利用经基因工程改造以同时表达单纯疱疹病毒1型胸苷激酶（HSV1-TK）和白细胞介素-13（IL-13）ζ链嵌合抗原受体（CAR）的CD8细胞毒性T淋巴细胞（CTL）进行免疫治疗是一种具有相当潜力的治疗策略。为了优化这种及相关免疫疗法，监测CTL的活力以及向胶质瘤细胞的迁移情况会有所帮助。我们表明，使用9-[4-[F]氟-3-(羟甲基)丁基]鸟嘌呤（[F]FHBG）进行的无创正电子发射断层扫描（PET）成像能够追踪CAR工程化CTL中存在的HSV1-tk报告基因表达。[F]FHBG成像安全，能够对患者体内稳定转染PET报告基因的T细胞进行纵向成像。进一步优化这种用于监测体内细胞迁移的成像方法应会极大地惠及各种基于细胞的癌症治疗方法。
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