title: 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.
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.
  
  
  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.
authors.affiliation: Department of Hematology and Oncology, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Kitawaki
authors.forename: Norimitsu
authors.initials: N
authors.lastname: Kadowaki
authors.forename: Keiko
authors.initials: K
authors.lastname: Fukunaga
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Kasai
authors.forename: Taira
authors.initials: T
authors.lastname: Maekawa
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Ohmori
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Itoh
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Kuzushima
authors.forename: Tadakazu
authors.initials: T
authors.lastname: Kondo
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Uchiyama
mesh_terms: D000208:Acute Disease; D000368:Aged; D017209:Apoptosis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045142:Cross-Priming / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005260:Female; D005334:Fever / Q000209:etiology; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D020014:K562 Cells; D007938:Leukemia / Q000276:immunology / Q000473:pathology; D007951:Leukemia, Myeloid / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D010844:Picibanil / Q000008:administration & dosage / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010844:Picibanil