PMID- 8932011
OWN - NLM
STAT- MEDLINE
DCOM- 19970303
LR  - 20191101
IS  - 1269-3286 (Print)
IS  - 1269-3286 (Linking)
VI  - 38
IP  - 2
DP  - 1996 Apr
TI  - Gene transfer applied to the modulation of alloreactivity.
PG  - 221-4
AB  - Allogenic hematopoietic stem cell transplantation is associated with a severe 
      complication induced by the T-cells present in the graft: graft-vs-host disease 
      (GVHD). While effectively preventing GVHD, ex vivo T-lymphocyte depletion of the 
      graft unfortunately increases graft rejection and reduces the graft-vs-leukemia 
      (GVL) effect. The ex vivo transfer to the herpes simplex thymidine kinase (HS-tk) 
      suicide gene into T-cells before their infusion with the hematopoietic stem cells 
      should allow for selective in vivo depletion of these T-cells with ganciclovir 
      (GCV) if subsequent GVHD was to occur. In patients not experiencing GVHD, and 
      therefore at a higher risk of relapse, one could preserve the beneficial effects 
      of the donor T-cells on tumor control. Lastly, the early presence of donor 
      T-cells in all patients should contribute to successful engraftment. We have 
      demonstrated that retroviral-mediated transfer of HS-tk and Neomycine resistance 
      genes in T-lymphocytes, followed by G418 selection, results in T-cells 
      specifically inhibited by GCV with no bystander effect. In a phase I study, 
      escalating amounts of HS-tk expressing T-cells will be infused in conjunction 
      with a T-cell depleted marrow graft to allogenic HLA identical recipients. 
      Toxicity, survival, alloreactivity and GCV-sensitivity of the gene-modified cells 
      will be monitored. If successful, such an approach could significantly contribute 
      to expanding the use of alloreactivity as a treatment modality.
FAU - Tiberghien, P
AU  - Tiberghien P
AD  - Laboratoire de Therapeutique, Service d'Hematologie, CHU, Besancon, France.
FAU - Cahn, J Y
AU  - Cahn JY
FAU - Contassot, E
AU  - Contassot E
FAU - Ferrand, C
AU  - Ferrand C
FAU - Reynolds, C W
AU  - Reynolds CW
FAU - Herve, P
AU  - Herve P
LA  - eng
PT  - Journal Article
PT  - Review
PL  - France
TA  - Hematol Cell Ther
JT  - Hematology and cell therapy
JID - 9613253
RN  - EC 2.7.1.21 (Thymidine Kinase)
SB  - IM
MH  - *Gene Transfer Techniques
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Humans
MH  - Leukemia/therapy
MH  - Simplexvirus/enzymology
MH  - Thymidine Kinase/genetics
MH  - Transplantation, Homologous
RF  - 25
EDAT- 1996/04/01 00:00
MHDA- 1996/04/01 00:01
CRDT- 1996/04/01 00:00
PHST- 1996/04/01 00:00 [pubmed]
PHST- 1996/04/01 00:01 [medline]
PHST- 1996/04/01 00:00 [entrez]
AID - 10.1007/s00282-996-0221-7 [doi]
PST - ppublish
SO  - Hematol Cell Ther. 1996 Apr;38(2):221-4. doi: 10.1007/s00282-996-0221-7.