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 patients

The use of antigen-presenting dendritic cells (DCs) is currently proposed f or tumor inmunotherapy through generation of CTLs to tumor antigens in canc er patients. In this study, DCs mere differentiated using granulocyte-macro phage colony-stimulating factor and tumor necrosis factor-cu from CD34(+) h ematopoietic progenitor cells that had been mobilized into the peripheral b lood. To use the phagocytic activity of DCs for processing and presentation of tumor antigens, we established DC clusters containing immature DCs by p reserving proliferating cell clusters without mechanical disruption. After an Ii-day culture, the developed clusters contained not only typical mature DCs but also immature DCs that showed active phagocytosis of latex particl es, suggesting that the clusters consisted of DCs of different maturational stages. These heterogeneous clusters could present an exogenous protein an tigen, 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 C TLs, The mechanical disruption of clusters abrogated the induction of CTLs to Leukemic cells as well as to hemocyanin, This observation gives an impor tant information for the use of heterogeneous DC clusters derived from auto logous peripheral blood CD34(+) cells in the case of immunotherapy for leuk emia.