Stimulation of autologous proliferative and cytotoxic T-cell responses by "leukemic dendritic cells" derived from blast cells in acute myeloid leukemia

Effective presentation of tumor antigens is fundamental to strategies aimed at enrolling the immune system in eradication of residual disease after co nventional treatments. Myeloid malignancies provide a unique opportunity to derive dendritic cells (DCs), functioning antigen-presenting cells, from t he malignant cells themselves. These may then co-express leukemic antigens together with appropriate secondary signals and be used to generate a speci fic, antileukemic immune response. In this study, blasts from 40 patients w ith acute myeloid leukemia (AML) were cultured with combinations of granulo cyte-macrophage colony-stimulating factor, interleukin 4, and tumor necrosi s factor alpha and development to DCs was assessed. After culture, cells fr om 24 samples exhibited morphological and immunophenotypic features of DCs, including expression of major histocompatibility complex class II, CD1a, C D83, and CD86, and were potent stimulators in an allogeneic mixed lymphocyt e reaction (MLR). Stimulation of autologous T-cell responses was assessed b y the proliferative response of autologous T cells to the leukemic DCs and by demonstration of the induction of specific, autologous, antileukemic cyt otoxicity. Of 17 samples, 11 were effective stimulators in the autologous M LR, and law, but consistent, autologous, antileukemic cytotoxicity was indu ced in 8 of 11 cases (mean, 27%; range, 17%-37%). This study indicates that cells with enhanced antigen-presenting ability can be generated from AML b lasts, that these cells can effectively prime autologous cytotoxic T cells in vitro, and that they may be used as potential vaccines in the immunother apy of AML. (Blood. 2001; 97:2764-2771) (C) 2001 by The American Society of Hematology.