Adoptive transfer of minor histocompatibility antigen-specific T lymphocytes eradicates leukemia cells without causing graft-versus-host disease

Adoptive transfer of T cells reactive to minor histocompatibility antigens has the unmatched ability to eradicate malignant hematopoietic cells. Unfor tunately, its use is hampered by the associated graft-versus-host disease. The critical issue of a possible dissociation of the antileukemic effect an d graft-versus-host disease by targeting specific minor histocompatibility antigens remains unresolved because of the unknown nature and number of min or histocompatibility antigens necessary or sufficient to elicit anti-leuke mic activity and graft-versus-host disease. We found that injection of T ly mphocytes primed against a single major histocompatibility complex class I- restricted immunodominant minor histocompatibility antigen (B6(dom1)) cause d no graft-versus-host disease but produced a curative anti-leukemic respon se. Avoidance of graft-versus-host disease required that no other host-reac tive T cells be co-injected with T cells primed with B6(dom1). Here we show that effective and non-toxic immunotherapy of hematologic malignancies can be achieved by targeting a single immunodominant minor histocompatibility antigen.