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Mol Ther. 2015 Jun;23(6):1110-1122. doi: 10.1038/mt.2015.48. Epub 2015 Mar 25.

[(18)F]FHBG PET/CT Imaging of CD34-TK75 Transduced Donor T Cells in Relapsed Allogeneic Stem Cell Transplant Patients: Safety and Feasibility.

Author information

1
Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.
2
Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri, USA.
3
Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA.
4
Department of Radiology Cyclotron Facility, Washington University School of Medicine, St. Louis, Missouri, USA.
5
Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA; Division of Nuclear Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
6
Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA; The Genome Institute, Washington University School of Medicine, St. Louis, Missouri, USA.
7
The Genome Institute, Washington University School of Medicine, St. Louis, Missouri, USA.
8
Department of Medicine, University of Michigan, Ann Arbor, MI, USA.
9
Department of Biology, Culver-Stockton College, Canton, Missouri, USA.
10
Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA; Department of Radiology Cyclotron Facility, Washington University School of Medicine, St. Louis, Missouri, USA; Department of Cancer Systems Imaging and MD Anderson Cancer Center, Houston, Texas, USA.
11
Department of Medical and Molecular Genetics, Indiana University, and the Indiana University Viral Production Facility (IU VPF), Indianapolis, Indiana, USA.
12
Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri, USA. Electronic address: jdipersi@dom.wustl.edu.

Abstract

Described herein is a first-in-man attempt to both genetically modify T cells with an imagable suicide gene and track these transduced donor T cells in allogeneic stem cell transplantation recipients using noninvasive positron emission tomography/computerized tomography (PET/CT) imaging. A suicide gene encoding a human CD34-Herpes Simplex Virus-1-thymidine kinase (CD34-TK75) fusion enabled enrichment of retrovirally transduced T cells (TdT), control of graft-versus-host disease and imaging of TdT migration and expansion in vivo in mice and man. Analysis confirmed that CD34-TK75-enriched TdT contained no replication competent γ-retrovirus, were sensitive to ganciclovir, and displayed characteristic retroviral insertion sites (by targeted sequencing). Affinity-purified CD34-TK75(+)-selected donor T cells (1.0-13 × 10(5))/kg were infused into eight patients who relapsed after allogeneic stem cell transplantation. Six patients also were administered 9-[4-((18)F)fluoro-3-hydroxymethyl-butyl]guanine ([(18)F]FHBG) to specifically track the genetically modified donor T cells by PET/CT at several time points after infusion. All patients were assessed for graft-versus-host disease, response to ganciclovir, circulating TdT cells (using both quantitative polymerase chain reaction and [(18)F]FHBG PET/CT imaging), TdT cell clonal expansion, and immune response to the TdT. This phase 1 trial demonstrated that genetically modified T cells and [(18)F]FHBG can be safely infused in patients with relapsed hematologic malignancies after allogeneic stem cell transplantation.

PMID:
25807290
PMCID:
PMC4817759
DOI:
10.1038/mt.2015.48
[Indexed for MEDLINE]
Free PMC Article

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