@article{613b76c44c784372a9660caeba128666,
title = "FHBG PET/CT imaging of CD34-TK75 transduced donor T cells in relapsed allogeneic stem cell transplant patients: Safety and feasibility",
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.",
author = "Eissenberg, {Linda G.} and Rettig, {Michael P.} and Ritchey, {Julie K.} and Prior, {Julie L.} and Schwarz, {Sally W.} and Jennifer Frye and White, {Brian S.} and Fulton, {Robert S.} and Armin Ghobadi and Cooper, {Matthew L.} and Couriel, {Daniel R.} and Seegulam, {Muhammad Esa} and David Piwnica-Worms and Farrokh Dehdashti and Kenneth Cornetta and DiPersio, {John F.}",
note = "Funding Information: We would like to acknowledge all donors and patients who participated in the trial at Barnes-Jewish Hospital in St. Louis. We thank Dr. Sam Gambhir for providing early guidance on protocol development for the clinical translation of [ 18 F]FHBG into patient trials. Mice were imaged and scans were analyzed in the Washington University (WU) Preclinical PET/CT Imaging Facility with the assistance of Lori Strong, Nichole Fettig, Ann Stroncek, Amanda Roth, and Margaret Morris. The WU Cyclotron Facility prepared the 18 FHBG. The Indiana University Vector Production Facility produced our master cell bank and a clinical grade viral supernatant. Transduction of the cells occurred in the WU Biological Therapy Core Facility under cGMP conditions with the assistance of Heather Missey and William Swaney. Transcriptome profiles of non-malignant T cell RNA-seq data were generously provided by Drs. Timothy Ley and analyzed by Dr. David Spencer (WU). Dr. Lee Ratner (WU) provided advice on development of the LM-PCR technique. We would further like to acknowledge the support of the following grants to the indicated individuals: NIH/NCI R01 CA83845 (PI: JFD), NIH/NCE R01 CA110489 (PI: JFD), NIH P50 CA094056-09 (PI: DPW and S. Achilefu, Project 4 PI: JFD), Barnes-Jewish Hospital Foundation Award 7603–55 (PI: JFD), and Siteman Cancer Center/Barnes-Jewish Hospital Foundation: Cancer Frontier Research Development Award (PI:JFD). The authors report no conflicts of interest. Publisher Copyright: {\textcopyright} 2015 The American Society of Gene & Cell Therapy.",
year = "2015",
month = jun,
day = "1",
doi = "10.1038/mt.2015.48",
language = "English",
volume = "23",
pages = "1110--1122",
journal = "Molecular Therapy",
issn = "1525-0016",
number = "6",
}