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Presentation of Tumor Antigens by Phagocytic Dendritic Cell Clusters Generated from Human CD34⁺ Hematopoietic Progenitor Cells

Induction of Autologous Cytotoxic T Lymphocytes against Leukemic Cells in Acute Myelogenous Leukemia Patients¹

The Center for Bone Marrow Transplantation and Immunotherapy, Institute for Clinical Research, Kumamoto National Hospital, Kumamoto 860-0008 [S-i. F., K. F., F. K.]; Second Department of Anatomy [K. S., T. E., K. M.] and Second Department of Internal Medicine [M. K.], Kumamoto University School of Medicine, Kumamoto 860-0811; Kitano Hospital Tazuke Kofukai Medical Research Institute, Osaka 530-0026 [K. T.], Japan

The use of antigen-presenting dendritic cells (DCs) is currently proposed for tumor immunotherapy through generation of CTLs to tumor antigens in cancer patients. In this study, DCs were differentiated using granulocyte-macrophage colony-stimulating factor and tumor necrosis factor- from CD34⁺ hematopoietic progenitor cells that had been mobilized into the peripheral blood. To use the phagocytic activity of DCs for processing and presentation of tumor antigens, we established DC clusters containing immature DCs by preserving proliferating cell clusters without mechanical disruption. After an 11-day culture, the developed clusters contained not only typical mature DCs but also immature DCs that showed active phagocytosis of latex particles, suggesting that the clusters consisted of DCs of different maturational stages. These heterogeneous clusters could present an exogenous protein antigen, keyhold limpet hemocyanin, to both CD4⁺ and CD8⁺ T lymphocytes. Furthermore, in three acute myelogeneous leukemia patients, clusters pulsed with autologous irradiated leukemic cells could also induce antileukemic CTLs. The mechanical disruption of clusters abrogated the induction of CTLs to leukemic cells as well as to hemocyanin. This observation gives an important information for the use of heterogeneous DC clusters derived from autologous peripheral blood CD34⁺ cells in the case of immunotherapy for leukemia.

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