1. [ 18 F]FHBG PET/CT Imaging of CD34-TK75 Transduced Donor T Cells in Relapsed Allogeneic Stem Cell Transplant Patients: Safety and Feasibility
- Author
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Brian S. White, Julie Ritchey, Daniel R. Couriel, Julie L. Prior, Muhammad Esa Seegulam, Matthew L. Cooper, Jennifer Frye, Linda Eissenberg, David Piwnica-Worms, Robert S. Fulton, Kenneth Cornetta, John F. DiPersio, Michael P. Rettig, Sally W. Schwarz, Armin Ghobadi, and Farrokh Dehdashti
- Subjects
Ganciclovir ,Guanine ,T-Lymphocytes ,CD34 ,Graft vs Host Disease ,Antigens, CD34 ,Pilot Projects ,Herpesvirus 1, Human ,Thymidine Kinase ,Mice ,Immune system ,Antigen ,Transduction, Genetic ,Cell Line, Tumor ,Drug Discovery ,Genetics ,Animals ,Humans ,Transplantation, Homologous ,Medicine ,Molecular Biology ,Pharmacology ,business.industry ,Suicide gene ,Flow Cytometry ,Virology ,3. Good health ,Transplantation ,Treatment Outcome ,Cell culture ,Positron-Emission Tomography ,Leukocytes, Mononuclear ,NIH 3T3 Cells ,Cancer research ,Feasibility Studies ,Molecular Medicine ,Original Article ,Stem cell ,business ,Stem Cell Transplantation ,medicine.drug - 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.
- Published
- 2015
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