Syngeneic/Autologous Graft-vs-Host Disease: Mobilization of Autoimmune Mechanisms as Antitumor Immunotherapy.
Autologous bone marrow transplantation (BMT) is a therapeutic option for the treatment of neoplastic disease. The rate of tumor recurrence after autologous BMT remains unacceptably high and is presumably due to the absence of the antitumor effect of graft-vs-host disease (GVHD). Recent studies indicate that administration of the immunosuppressive drug cyclosporine (CsA) after syngeneic/autologous BMT elicits an autoimmune syndrome with pathology virtually identical to GVHD. This syndrome, termed syngeneic/autologous GVHD, can be induced in humans and rodent models and is associated with the development of cytolytic autoreactive T cells that recognize MHC class II determinants. Current studies in the rat model and preliminary clinical trials suggest that syngeneic/autologous GVHD provides a significant antitumor effect. This antitumor effect can be enhanced by the administration of either (-interferon, which upregulates the antigen recognized by the autoreactive effector cells, or IL-2, which amplifies the effector mechanisms of syngeneic/autologous GVHD. Mobilization of autoimmune mechanisms that mediate syngeneic/autologous GVHD may be a promising immunotherapeutic approach for certain human neoplastic diseases.
Hess
AD
Bone Marrow Transplant Unit, The Johns Hopkins University, Baltimore, Maryland 21287, USA.