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.

Abstract:

: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.

journal_name

Leuk Lymphoma

journal_title

Leukemia & lymphoma

authors

Fujii S,Shimizu K,Fujimoto K,Kiyokawa T,Tsukamoto A,Sanada I,Kawano F

doi

10.3109/10428190109064592

keywords:

subject

Has Abstract

pub_date

2001-07-01 00:00:00

pages

357-69

issue

3

eissn

1042-8194

issn

1029-2403

journal_volume

42

pub_type

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