249 Preclinical Development of Cord Blood-Derived Dendritic Cell-Based Immunotherapies after Hematopoietic Cell Transplantation in Children with AML

Track: Poster Abstracts
Wednesday, February 11, 2015, 6:45 PM-7:45 PM
Grand Hall CD (Manchester Grand Hyatt)
Colin de Haar, PhD , Applied Tumor Immunology Section, Lab Translational Immunology, UMC Utrecht, Utrecht, Netherlands
Maud Plantinga, PhD , Applied Tumor Immunology Section, Lab Translational Immunology, UMC Utrecht, Utrecht, Netherlands
Nina Blokland , Applied Tumor Immunology Section, Lab Translational Immunology, UMC Utrecht, Utrecht, Netherlands
Ester Dunnebach , Applied Tumor Immunology Section, Lab Translational Immunology, UMC Utrecht, Utrecht, Netherlands
Marianne Boes, PhD , Applied Tumor Immunology Section, Lab Translational Immunology, UMC Utrecht, Utrecht, Netherlands
Jaap-Jan Boelens, MD, PhD , Pediatric Blood and Marrow Transplantation Program, University Medical Center Utrecht, Utrecht, Netherlands
Stefan Nierkens, PhD , Applied Tumor Immunology Section, Lab Translational Immunology, UMC Utrecht, Utrecht, Netherlands
Presentation recording not available for download or distribution as requested by the presenting author.
Pediatric patients with refractory/relapsed acute myeloid leukemia (AML) have only one treatment option: hematopoietic cell transplantation (HCT). Using cord blood (CB)-derived stem cells, instead of cells from bone marrow cells or peripheral blood, results in less relapses (increased anti-tumor reactivity) and less graft-versus-host disease (increased safety). Although this treatment is potentially curative, still more than half of the children die from relapses. We therefore aim to develop additional powerful and safe CB-derived immunotherapies for pediatric AML.

First, we developed a dendritic cell (DC) vaccine, derived from the CB stem cells with the goal to stimulate the anti-tumor reactivity of the newly developing immune system in AML patients after CB-HCT. CD34+ CB stem cells were expanded and differentiated into DCs. CBDCs upregulated co-stimulatory molecules after maturation and showed enhanced CCR7-dependent migration towards CCL19 in a trans-well migrations assay. In addition, CBDCs expressed the tumor antigen Wilms’ Tumor 1 (WT1) protein after electroporation with WT1-mRNA. These WT1 expressing CBDCs were not only able to stimulate T cells in a mixed lymphocyte reaction but in an antigen-specific setting as well.

Second, we are testing additional immunotherapies that can be used combined with CBDC vaccination, i.e. NK cells and gamma delta T cells.  All of which may either enhance the immune stimulating function of the CBDCs, or can be activated by CBDCs to directly and/or indirectly target the AML cells. As such, these addition immunotherapies will further intensify the anti-tumor reactivity of CB-HCT and not only in the AML setting but potentially also in several solid tumors.

Disclosures:
Nothing To Disclose
See more of: Poster Session 1: Leukemia
See more of: Poster Abstracts