Use of Donor T-Lymphocytes Expressing Herpes-Simplex Thymidine Kinase in Allogeneic Bone Marrow Transplantation: A Phase I–II Study. Laboratorie d'Histocompatibilité et Thérapeutique Immuno-Moléculaire, Besançon, France
- 20 March 1997
- journal article
- research article
- Published by Mary Ann Liebert Inc in Human Gene Therapy
- Vol. 8 (5), 615-624
- https://doi.org/10.1089/hum.1997.8.5-615
Abstract
Allogeneic bone marrow transplantation (BMT) is associated with a severe complication; graft-versus-host disease (GvHD). While effectively preventing GvHD, ex-vivo T lymphocyte marrow depletion unfortunately increases graft rejection and reduces the graft-ver-sus-leukemia (GvL) effect. The ex-vivo transfer of the herpes simplex thymidine kinase (HS-tk) suicide gene into T cells before their infusion with hematopoietic stem cells should allow for selective in vivo depletion of these T cells with ganciclovir (GCV) if subsequent GvHD was to occur. Thus, one could preserve the beneficial effects of the T cells on engraftment and tumor control in patients not experiencing severe GvHD. We have demonstrated that retroviral-mediated transfer of HS-tk and Neomycin resistance genes in T-lymphocytes followed by G418 selection results in T-cells specifically inhibited by GCV with no bystander effect. Escalating amounts of HS-tk expressing T-cells will be infused in conjunction with a T-cell depleted marrow grafts to allogeneic HLA identical leukemic recipients. Toxicity, survival, alloreactivity and GCV-sensitivity of the gene-modified cells will be monitored. Patients with leukemia undergoing an HLA-matched allogeneic BMT associated with a high risk of GvHD will be enrolled in the protocol.Keywords
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