FHBG PET/CT imaging of CD34-TK75 transduced donor T cells in relapsed allogeneic stem cell transplant patients: Safety and feasibility

Linda G. Eissenberg, Michael P. Rettig, Julie K. Ritchey, Julie L. Prior, Sally W. Schwarz, Jennifer Frye, Brian S. White, Robert S. Fulton, Armin Ghobadi, Matthew L. Cooper, Daniel R. Couriel, Muhammad Esa Seegulam, David Piwnica-Worms, Farrokh Dehdashti, Kenneth Cornetta, John F. DiPersio

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1110-1122
Number of pages13
JournalMolecular Therapy
Volume23
Issue number6
DOIs
StatePublished - Jun 1 2015

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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