Cellular engineering of HSV-tk transduced, expanded T lymphocytes for graft-versus-host disease management.
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.
Advanced Cell and Gene Therapy, Chapel Hill, NC 27516, USA. sburger@ac-gt.com
Scott R
SR
Burger
Diane M
DM
Kadidlo
Lisa
L
Basso
Nancy
N
Bostrom
Paul J
PJ
Orchard
D019264:Adoptive Transfer / Q000009:adverse effects / Q000379:methods; D041722:Genes, Transgenic, Suicide / Q000235:genetics*; D006086:Graft vs Host Disease / Q000276:immunology / Q000628:therapy*; D006801:Humans; D018139:Simplexvirus / Q000235:genetics*; D013601:T-Lymphocytes / Q000502:physiology*; D013937:Thymidine Kinase / Q000235:genetics*
D013937:Thymidine Kinase