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Gene transfer applied to the modulation of alloreactivity.
- Source :
-
Hematology and cell therapy [Hematol Cell Ther] 1996 Apr; Vol. 38 (2), pp. 221-4. - Publication Year :
- 1996
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 1269-3286
- Volume :
- 38
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Hematology and cell therapy
- Publication Type :
- Academic Journal
- Accession number :
- 8932011
- Full Text :
- https://doi.org/10.1007/s00282-996-0221-7