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Updated: Sep 21, 2026

Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade
11:55

Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade

Published on: March 14, 2011

[Modulation of alloreactivity using genetically modified T lymphocytes]

P Tiberghien1

  • 1Laboratoire de Thérapeutique Immuno-moléculaire, Etablissement de Transfusion Sanguine de Franche-Comté, Besançon.

Transfusion Clinique Et Biologique : Journal De La Societe Francaise De Transfusion Sanguine
|January 1, 1997
PubMed

While effectively preventing graft-versus-host disease (GVHD), ex vivo T-lymphocyte depletion of the graft unfortunately increases graft rejection and reduces the graft-versus-leukemia (GVL) effect after allogeneic hematopoietic stem cell transplantation. The ex vivo transfer of 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. 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 are infused in conjunction with a T-cell depleted marrow graft to allogeneic HLA identical recipients. Toxicity, survival alloreactivity and GCV-sensitivity of the gene-modified cells are monitored.

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