Reporter gene imaging of targeted T cell immunotherapy in recurrent glioma

TY - JOUR

T1 - Reporter gene imaging of targeted T cell immunotherapy in recurrent glioma

AU - Keu, K.V.

AU - Witney, Timothy H.

AU - Yaghoubi, S.

AU - Rosenberg, J.

AU - Kurien, A.

AU - Magnusson, R.

AU - Williams, J.

AU - Habte, F.

AU - Wagner, J.R.

AU - Forman, S.

AU - Brown, C.

AU - Allen-Auerbach, M.

AU - Czernin, J.

AU - Tang, W.

AU - Jensen, M.C.

AU - Badie, B.

AU - Gambhir, S.S.

PY - 2017/1/18

Y1 - 2017/1/18

N2 - 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-[18F]fluoro-3-(hydroxymethyl)butyl] guanine ([18F]FHBG) can track HSV1-tk reporter gene expression present in CAR-engineered CTLs. [18F]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. © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.

AB - 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-[18F]fluoro-3-(hydroxymethyl)butyl] guanine ([18F]FHBG) can track HSV1-tk reporter gene expression present in CAR-engineered CTLs. [18F]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. © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.

U2 - 10.1126/scitranslmed.aag2196

DO - 10.1126/scitranslmed.aag2196

M3 - Article

SN - 1946-6234

VL - 9

JO - Science Translational Medicine

JF - Science Translational Medicine

IS - 373

M1 - eaag2196

ER -