New generation dendritic cell vaccine for immunotherapy of acute myeloid leukemia

Autor: Miran Javorovic, Dolores J. Schendel, Gunnar Kvalheim, Marion Subklewe, Felix S. Lichtenegger, Christiane Geiger, Iris Bigalke
Rok vydání: 2014
Předmět:
Zdroj: Cancer Immunology, Immunotherapy. 63:1093-1103
ISSN: 1432-0851
0340-7004
DOI: 10.1007/s00262-014-1600-5
Popis: 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.
Databáze: OpenAIRE
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