Adoptive transfer of allogeneic tumor-specific T cells mediates effective regression of large tumors across major histocompatibility barriers.

摘要: Graft-versus-tumor effects can be achieved after allogeneic bone marrow transplantation in patients with malignancies of the kidney or hematopoietic system but are often accompanied by severe graft-versus-host-disease (GVHD). We sought to maximize graft-versus-tumor while minimizing GVHD using tumor-specific effector T cells rather than open-repertoire cells. transferred CD8+ pmel-1 CD4+ TRP-1 specific for melanoma-associated antigens, glycoprotein 100 (gp100) and tyrosinase-related protein-1 (TRP-1), respectively, into B16-melanoma–bearing mice. Mice receiving a preparative regimen nonmyeloablating (5 Gy) total body irradiation experienced rapid rejection lymphocytes no impact on tumor growth. However, when mice were given more intense conditioning regimens combined autologous transplantation, adoptively persisted at detectable levels several weeks mediated significant regression large, vascularized tumors. found that risk was low toxicity observed only substantial numbers open repertoire naive mixed lymphocytes. Taken together, these data indicate use result antitumor absence measurable GVHD.