Cancer Immunology, Immunotherapy

, Volume 63, Issue 10, pp 1093–1103 | Cite as

New generation dendritic cell vaccine for immunotherapy of acute myeloid leukemia

  • Marion Subklewe
  • Christiane GeigerEmail author
  • Felix S. Lichtenegger
  • Miran Javorovic
  • Gunnar Kvalheim
  • Dolores J. Schendel
  • Iris Bigalke
Focussed Research Review


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.


AML Cancer immunotherapy Clinical trial Dendritic cells Vaccine PIVAC 13 



Acute myeloid leukemia


Bone marrow


Cytotoxic T lymphocytes


Dendritic cells


Good manufacturing practice


Human cytomegalovirus


Hematopoietic stem cell


Hematopoietic stem cell transplantation


In vitro-transcribed


Leukemia-associated antigen


Leukemic stem cell


Multiparameter flow cytometry


Minimal residual disease


Natural killer


Overall survival


Peripheral blood


Peripheral blood mononuclear cells


Preferentially expressed antigen in melanoma


Relapse-free survival


Real-time quantitative polymerase chain reaction


Tumor-associated antigen


T helper 1


Toll-like receptor


Wilm’s tumor protein 1



We thank Frauke Schnorfeil for help with Figs. 1 and 2. This work was supported in part by funds from BayImmuNet, the Bavarian Immunotherapy Network (, and the Helmholtz Alliance for Immunotherapy of Cancer.

Conflict of interest

Dolores J. Schendel is Managing Director of Trianta Immunotherapies GmbH and Chief Scientific Officer of Medigene AG. Christiane Geiger is Associate Director of DC Vaccine Development of Trianta Immunotherapies GmbH. All other authors declare that they have no conflicts of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Marion Subklewe
    • 1
  • Christiane Geiger
    • 2
    • 4
    Email author
  • Felix S. Lichtenegger
    • 1
  • Miran Javorovic
    • 2
  • Gunnar Kvalheim
    • 3
  • Dolores J. Schendel
    • 2
    • 4
  • Iris Bigalke
    • 2
    • 3
  1. 1.Department of Internal Medicine IIIKlinikum der Universität MünchenMunichGermany
  2. 2.Institute of Molecular ImmunologyHelmholtz Zentrum MünchenMunichGermany
  3. 3.Department of Cellular TherapyOslo University HospitalOsloNorway
  4. 4.Trianta Immunotherapies GmbHA subsidiary of Medigene AGPlanegg-MartinsriedGermany

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