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

Leuk Lymphoma. 2001 Jul;42(3):357-69. doi: 10.3109/10428190109064592.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / analysis
  • Cytotoxicity, Immunologic
  • Dendritic Cells / immunology
  • Dendritic Cells / transplantation*
  • Female
  • Graft vs Host Disease / prevention & control
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation*
  • Histocompatibility Testing
  • Humans
  • Hypersensitivity, Delayed
  • Immunophenotyping
  • Interleukin-2 / therapeutic use
  • Lymphocyte Culture Test, Mixed
  • Lymphocyte Subsets / immunology
  • Lymphocyte Transfusion
  • Male
  • Middle Aged
  • Recurrence
  • Skin Tests
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation*
  • Transplantation, Homologous

Substances

  • Antigens, CD
  • Interleukin-2
  • Granulocyte-Macrophage Colony-Stimulating Factor