PMID- 15638716 OWN - NLM STAT- MEDLINE DCOM- 20050524 LR - 20191109 IS - 1566-5232 (Print) IS - 1566-5232 (Linking) VI - 5 IP - 1 DP - 2005 Feb TI - T cell suicide gene therapy to aid haematopoietic stem cell transplantation. PG - 121-32 AB - Graft versus host disease (GVHD) is a T cell mediated phenomenon that arises following allogeneic haematopoietic stem cell transplantation, and may be particularly severe in the context of human leukocyte antigen (HLA) mismatched procedures. Although GVHD can be largely abrogated through T cell depletion, such measures result in loss of graft potency and reduced anti-viral and anti-leukaemic effects. The genetic modification of T cells to carry a suicide gene mechanism has been advocated as means of allowing T cells to be harnessed for their beneficial effects, and safely eliminated in the event of significant GVHD. The feasibility of the strategy has been demonstrated in clinical studies using T cells modified by retroviral transduction to encode the herpes simplex thymidine kinase (HSVTK) gene to treat patients with haematological malignancies. However, a number of limitations associated with current protocols have become apparent. Most notably, the process of retroviral transduction, which requires pre-activation of T cells, appears to impair subsequent functional potential. Efforts are now directed towards circumventing the pre-activation requirements of retroviral vectors by using alternative lentiviral systems, in association with improved suicide gene/prodrug combinations. FAU - Qasim, W AU - Qasim W AD - Molecular Immunology Unit, Institute of Child Health, 30, Guilford Street, London WC1N 1EH, UK. W.Qasim@ich.ucl.ac.uk FAU - Gaspar, H B AU - Gaspar HB FAU - Thrasher, A J AU - Thrasher AJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United Arab Emirates TA - Curr Gene Ther JT - Current gene therapy JID - 101125446 SB - IM MH - Animals MH - *Genes, Transgenic, Suicide MH - Genetic Therapy/*methods MH - *Hematopoietic Stem Cell Transplantation MH - Humans MH - T-Lymphocytes/*immunology RF - 69 EDAT- 2005/01/11 09:00 MHDA- 2005/05/25 09:00 CRDT- 2005/01/11 09:00 PHST- 2005/01/11 09:00 [pubmed] PHST- 2005/05/25 09:00 [medline] PHST- 2005/01/11 09:00 [entrez] AID - 10.2174/1566523052997497 [doi] PST - ppublish SO - Curr Gene Ther. 2005 Feb;5(1):121-32. doi: 10.2174/1566523052997497.