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Use of Donor T-Lymphocytes Expressing Herpes-Simplex Thymidine Kinase in Allogeneic Bone Marrow Transplantation - a Phase I-Ii Study

  1. Author:
    Tiberghien, P.
    Cahn, J. Y.
    Brion, A.
    Deconinck, E.
    Racadot, E.
    Herve, P.
    Milpied, N.
    Lioure, B.
    Gluckman, E.
    Bordigoni, P.
    Jacob, W.
    Chiang, Y. W.
    Marcus, S.
    Reynolds, C.
    Longo, D.

  2. Author Address

    Tiberghien P ETABLISSEMENT TRANSF SANGUINE FRANCHE COMTE LAB HISTOCOMPATIBILITE & THERAPEUT IMMUNOMOL F-25000 BESANCON FRANCE CTR HOSP UNIV BESANCON SERV HEMATOL F-25000 BESANCON FRANCE CHU BESANCON F-25030 BESANCON FRANCE ETS FRANCHE COMTE BESANCON FRANCE CHU NANTES F-44035 NANTES 01 FRANCE CHU STRASBOURG F-67000 STRASBOURG FRANCE CHU SR LOUIS BONE MARROW TRANSPLANTAT UNIT PARIS FRANCE CHU NANCY BONE MARROW TRANSPLANTAT UNIT NANCY FRANCE GTI GAITHERSBURG, MD USA NCI FREDERICK, MD 21701 USA NIA BALTIMORE, MD 21224 USA
    1. Year: 1997
  2. Journal: Human Gene Therapy
    1. 8
    2. 5
    3. Pages: 615-624
  4. Type of Article: Article
  1. 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-versus-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. [References: 31]

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