title: New generation dendritic cell vaccine for immunotherapy of acute myeloid leukemia.
abstract: Dendritic cell (DC)-based immunotherapy is a promising strategy for the elimination of minimal residual disease in patients with acute myeloid leukemia (AML). Particularly, patients with a high risk of relapse who are not eligible for hematopoietic stem cell transplantation could benefit from such a therapeutic approach. Here, we review our extensive studies on the development of a protocol for the generation of DCs with improved immunogenicity and optimized for the use in cell-based immunotherapy. This new generation DC vaccine combines the production of DCs in only 3 days with Toll-like receptor-signaling-induced cell maturation. These mature DCs are then loaded with RNA encoding the leukemia-associated antigens Wilm's tumor protein 1 and preferentially expressed antigen in melanoma in order to stimulate an AML-specific T-cell-based immune response. In vitro as well as in vivo studies demonstrated the enhanced capacity of these improved DCs for the induction of tumor-specific immune responses. Finally, a proof-of-concept Phase I/II clinical trial is discussed for post-remission AML patients with high risk for disease relapse.
authors.affiliation: Department of Internal Medicine III, Klinikum der Universität München, Munich, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Subklewe
authors.forename: Christiane
authors.initials: C
authors.lastname: Geiger
authors.forename: Felix S
authors.initials: FS
authors.lastname: Lichtenegger
authors.forename: Miran
authors.initials: M
authors.lastname: Javorovic
authors.forename: Gunnar
authors.initials: G
authors.lastname: Kvalheim
authors.forename: Dolores J
authors.initials: DJ
authors.lastname: Schendel
authors.forename: Iris
authors.initials: I
authors.lastname: Bigalke
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000628:therapy*; D051379:Mice
chemical_list: D019496:Cancer Vaccines