Cellular engineering of HSV-tk transduced, expanded T lymphocytes for graft-versus-host disease management

Scott R. Burger, Diane M. Kadidlo, Lisa Basso, Nancy Bostrom, Paul J. Orchard

Research output: Contribution to journalReview article

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)121-131
Number of pages11
JournalActa Haematologica
Volume110
Issue number2-3
DOIs
StatePublished - Nov 11 2003

Keywords

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

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