Allo-major histocompatibility complex-restricted cytotoxic T lymphocytes engraft in bone marrow transplant recipients without causing graft-versus-host disease

Previous experiments in humans and mice have shown that allogeneic donors c an serve as a source of cytotoxic T lymphocytes (CTL) specific for proteins , such as cyclin-D1 and mdm-2, expressed at elevated levels in tumor cells. In vitro, allo-major histocompatibility complex (MHC)-restricted CTL again st these proteins selectively killed allogeneic tumor cells, including lymp homa, but not normal control cells. This suggested that these CTL may be us eful for adoptive tumor immunotherapy, provided that they (1) survive in MH C-disparate hosts, (2) maintain their killing specificity, and (3) do not a ttack normal host tissues. Here, we used cloned allo-restricted CTL isolate d from BALB/c mice (H-2(d)) that killed H-2(b)-derived tumor cells expressi ng elevated levels of the mdm-2 target protein, When these CTL were injecte d into bone marrow transplanted (BMT) C57BL/6 (H-2(b)) recipients, they con sistently engrafted and were detectable in lymphoid tissues and in the bone marrow (BM), Long-term survival was most efficient in spleen and lymph nod es, where CTL were found up to 14 weeks after injection. The administration of CTL did not cause graft-versus-host disease (GVHD) normally associated with injection of allogeneic T cells. These data show that allo-restricted CTL clones are promising reagents for antigen-specific immunotherapy in BMT hosts, because they engraft and retain their specific killing activity wit hout causing GVHD, (C) 1999 by The American Society of Hematology.