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 Geiger
  • Felix S. Lichtenegger
  • Miran Javorovic
  • Gunnar Kvalheim
  • Dolores J. Schendel
  • Iris Bigalke
Focussed Research Review

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.

Keywords

AML Cancer immunotherapy Clinical trial Dendritic cells Vaccine PIVAC 13 

Abbreviations

AML

Acute myeloid leukemia

BM

Bone marrow

CTL

Cytotoxic T lymphocytes

DC

Dendritic cells

GMP

Good manufacturing practice

hCMV

Human cytomegalovirus

HSC

Hematopoietic stem cell

HSCT

Hematopoietic stem cell transplantation

Ivt

In vitro-transcribed

LAA

Leukemia-associated antigen

LSC

Leukemic stem cell

MFC

Multiparameter flow cytometry

MRD

Minimal residual disease

NK

Natural killer

OS

Overall survival

PB

Peripheral blood

PBMC

Peripheral blood mononuclear cells

PRAME

Preferentially expressed antigen in melanoma

RFS

Relapse-free survival

RQ-PCR

Real-time quantitative polymerase chain reaction

TAA

Tumor-associated antigen

Th1

T helper 1

TLR

Toll-like receptor

WT1

Wilm’s tumor protein 1

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Marion Subklewe
    • 1
  • Christiane Geiger
    • 2
    • 4
  • 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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