Treatment of post-transplanted, relapsed patients with hematological malignancies by infusion of HLA-matched, allogeneic-dendritic cells (DCs) pulsed with irradiated tumor cells and primed T cells.
Patients with hematological malignancies who relapse after bone marrow transplantation (BMT) are often treated with donor lymphocyte infusion. However, this procedure often results in graft-versus-host disease (GVHD). While, Dendritic cells (DCs), which present antigens to naive T cells, have been used in the immunotherapy of cancer, this approach has been logistically difficult due to limiting numbers of DCs. We have now developed a method for obtaining a large number of DCs by treating the granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSCs) from healthy donors with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF-alpha). The resulting cells possess the morphologic, phenotypic, and functional characteristics of mature DCs. In in vitro studies, culture of these HLA-matched donor derived-DCs with irradiated each patient's tumor cells as an antigen source, followed by incubation with T cells from the patient, induced the production of highly cytotoxic T lymphocytes (CTLs) specific for the respective tumor cells in the semi-allogeneic setting. A transient, but objective clinical response was obtained in the absence of GVHD when we injected the DCs which had been pulsed with irradiated tumor cells as well as primed T cells from the same original donor of related- allogeneic stem cell transplantation into the relapsed patients. Our findings suggest that treatment of relapsed patients with such donor-derived DCs, and primed T cells may be effective as an adjunctive immunotherapy.
Fujii
S
S
Centre for Bone Marrow Transplantation and Immunotherapy, Institute for Clinical Research, Kumamoto National Hospital, 1-5 Ninomaru, Kumamoto 860-0008, Japan. fujii1018@aol.com
Shimizu
K
K
Fujimoto
K
K
Kiyokawa
T
T
Tsukamoto
A
A
Sanada
I
I
Kawano
F
F
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D006968:Hypersensitivity, Delayed; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000627:therapeutic use; D007959:Lymphocyte Culture Test, Mixed; D016131:Lymphocyte Subsets / Q000276:immunology; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012882:Skin Tests; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D014184:Transplantation, Homologous
D015703:Antigens, CD; D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor