Feasibility of Immunotherapy of Relapsed Leukemia With Ex Vivo–Generated Cytotoxic T Lymphocytes Specific for Hematopoietic System-Restricted Minor Histocompatibility Antigens
作者： Tuna Mutis , Rob Verdijk , Ellen Schrama , Bennie Esendam , Anneke Brand
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摘要: Allogeneic bone marrow transplantation (BMT) is a common treatment of hematologic malignancies. Recurrence the underlying malignancy major cause failure. Donor-derived cytotoxic T lymphocytes (CTLs) specific for patients’ minor histocompatibility antigens (mHags) play an important role in both graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) reactivities. mHags HA-1 HA-2 induce HLA-A*0201-restricted CTLs vivo are exclusively expressed on hematopoietic cells, including leukemic cells precursors, but not fibroblasts, keratinocytes, or liver cells. The chemical nature known. We investigated feasibility ex generation mHag HA-1– HA-2–specific from unprimed and/or HA-2–negative healthy blood donors. synthetic peptide-pulsed dendritic (DCs) were used as antigen-presenting (APC) to stimulate autologous CD8+ vivo–generated efficiently lyse derived acute myeloid leukemia (AML) lymphoid (ALL) patients. No lytic reactivity was detected against nonhematopoietic Sufficient numbers can be obtained adoptive immunotherapy purposes. In conclusion, we present feasible, novel therapy relapsed after BMT with low risk GVHD.
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