Feasibility of immunotherapy of relapsed leukemia with ex vivo-generated cytotoxic T lymphocytes specific for hematopoietic system-restricted minor histocompatibility antigens

Allogeneic bone marrow transplantation (BMT) is a common treatment of hemat ologic malignancies. Recurrence of the underlying malignancy is a major cau se of treatment failure. Donor-derived cytotoxic T lymphocytes (CTLs) speci fic for patients' minor histocompatibility antigens (mHags) play an importa nt role in both graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) reactivities, mHags HA-1 and HA-2 induce HLA-A*0201-restricted CTLs i n vivo and are exclusively expressed on hematopoietic cells, including leuk emic cells and leukemic precursors, but not on fibroblasts, keratinocytes, or liver cells. The chemical nature of the mHags HA-1 and HA-2 is known. We investigated the feasibility of ex vivo generation of mHag HA-1- and HA-a- specific CTLs from unprimed mHag HA-1- and/or HA-2-negative healthy blood d onors. HA-1 and HA-2 synthetic peptide-pulsed dendritic cells (DCs) were us ed as antigen-presenting cells (APC) to stimulate autologous unprimed CD8() T cells. The ex vivo-generated HA-1- and HA-2-specific CTLs efficiently l yse leukemic cells derived from acute myeloid leukemia (AML) and acute lymp hoid leukemia (ALL) patients. No lytic reactivity was detected against nonh ematopoietic cells. Sufficient numbers of the CTLs can be obtained for the adoptive immunotherapy purposes, In conclusion, we present a feasible, nove l therapy for the treatment for relapsed leukemia after BMT with a low risk of GVHD. (C) 1999 by The American Society of Hematology.