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Cross-priming of CD8+ T cells in vivo by dendritic cells pulsed with autologous apoptotic leukemic cells in immunotherapy for elderly patients with acute myeloid leukemia
- Source :
-
Experimental Hematology . Apr2011, Vol. 39 Issue 4, p424-433.e2. 0p. - Publication Year :
- 2011
-
Abstract
- Objective: The prognosis for elderly patients with acute myeloid leukemia (AML) remains dismal. To explore the potential of immunotherapy for improving clinical outcomes for these patients, we performed a phase I clinical trial of dendritic cell (DC)−based immunotherapy for elderly patients with AML. Materials and Methods: Autologus monocytes were obtained after reducing tumor burden by chemotherapy. Immature DCs induced with granulocyte-macrophage colony-stimulating factor and interleukin-4 were pulsed with autologous apoptotic leukemic cells as antigens. DCs were administered intradermally to four patients five times at 2-week intervals. To facilitate DC migration to lymph nodes, injection sites were pretreated with killed Streptococcus pyogenes OK-432 one day before. DCs were coinjected with OK-432 to induce maturation and interleukin-12 production in vivo. Results: Antileukemic responses were observed by an interferon-γ enzyme-linked immunospot assay or a tetramer assay in two of four patients. In a human leukocyte antigen−A∗2402-positive patient, induction of CD8+ T-cell responses to WT1- and human telomerase reverse transcriptase – derived peptides were observed, indicating cross-priming in vivo. The two patients with antileukemic immunity showed longer periods of disease stabilization than the other two patients. Conclusions: This study demonstrates the immunogenicity of autologous DCs that cross-present leukemia-associated antigens from autologous apoptotic leukemic cells in vivo in elderly patients with AML. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0301472X
- Volume :
- 39
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Experimental Hematology
- Publication Type :
- Academic Journal
- Accession number :
- 59456870
- Full Text :
- https://doi.org/10.1016/j.exphem.2011.01.001