Gene- and Immunotherapy for Hematological Diseases
Guest Editor: Dagmar Dilloo, Düsseldorf

Paper

Cellular Engineering of HSV-tk Transduced, Expanded T Lymphocytes for Graft-versus-Host Disease Management
Scott R. Burger^a, Diane M. Kadidlo^b, Lisa Basso^c,d, Nancy Bostrom^b, Paul J. Orchard<sup>c,d,e

a</sup>Advanced Cell and Gene Therapy, Chapel Hill, N.C. and Department of Laboratory Medicine and Pathology, University of Minnesota Medical School,
^bCell Therapy Clinical Laboratory, Fairview University Medical Center,
^cProgram in Blood and Marrow Transplantation,
^dDepartment of Pediatrics,
^eInstitute of Human Genetics, University of Minnesota Medical School, Minneapolis, Minn., USA

Address of Corresponding Author

Acta Haematol 2003;110:121-131 (DOI: 10.1159/000072461)

  Key Words

• HSV-tk
• Suicide genes
• Allogeneic T lymphocytes
• Graft-versus-host disease
• Cell therapy

  Abstract

Engineering donor T lymphocytes with inducible 'suicide genes', such as herpes simplex virus thymidine kinase, has potential to improve safety and efficacy in allogeneic transplantation by facilitating management of graft-versus-host disease. Elective administration of a relatively nontoxic pro-drug would induce in vivo negative selection of engineered lymphocytes specifically, sparing other donor hematopoietic cells. The engineered cells must retain immunologic function, and undergo negative selection in response to clinically attainable plasma concentrations of pro-drug. The cell engineering process itself, typically involving activation, transduction, ex vivo expansion, and selection, must produce clinically useful numbers of genetically modified cells at high purity. We discuss development of a cellular engineering manufacturing process that yields transduced, expanded T lymphocytes meeting these requirements.

Copyright © 2003 S. Karger AG, Basel

  Author Contacts

Scott R. Burger, MD
Advanced Cell & Gene Therapy
105 Highgrove Drive
Chapel Hill, NC 27516 (USA)
Tel./Fax +1 919 969 1103, E-Mail sburger@ac-gt.com

  Article Information

Number of Print Pages : 11
Number of Figures : 8, Number of Tables : 4, Number of References : 37