For many tumors derived from the hematopoietic system, allogeneic bone marrow transplant is the treatment of choice. T cells as well as some other unidentified cells in the bone marrow, mount a reaction against the malignant cells and result in tumor cell killing. However, a life-threatening complication of this effective therapy is the development of graft versus host disease (GVHD) whereby the effector cells in the bone marrow attack various cells and structures of the recipient (host) of the bone marrow. The incidence of severe GVHD can be avoided by removing the T cells from the bone marrow prior to its administration to the host. With the removal of these cells, however, the effectiveness of the bone marrow transplant is markedly reduced and the chance of recurrence, graft rejection and activation of endogenous viral infections is markedly increased. Therefore, it is clear that these cells play an important part in the treatment of the hematologic malignancy by bone marrow transplantation. Bonini et al, have developed a strategy to eliminate these cells in the body of the host when GVHD occurs. The Herpes Simplex Virus (HSV) has a suicide gene (thymidine kinase) susceptible to the drug, ganciclovir. These authors introduced this gene (HSV-TK) into the bone marrow lymphocytes prior to their administration to patients. The lymphocytes were also transfected with a truncated form of the nerve growth factor receptor expressed on the cell surface. This transfection allowed in vitro selection of the transduced cells. In vivo, such expression made it possible to detect and characterize the transduced cells by fluorescence-activated cell sorting. These cells survived in patients up to 12 months and in 5/12 patients exhibited anti-tumor activity. When the GVHD occurred, the disease could effectively be controlled by the administration of the ganciclovir. The drug led to the elminiation of the tranduced cells in the host. Such strategy is likely to increase the effectiveness and safety of the bone marrow transplant in patients who require allogeneic bone marrow transplant.

REFERENCES:

Bonini C, 1997           [See Related Articles]
HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia
Science 276(5319), 1719-1724 (1997)

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