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Dendritic cell vaccination after cord blood cell transplantation

Tuesday 5 January 2016

Nierkens/Boelens Lab

Project
Survival rates for childhood cancer have improved significantly over the last decade. However, certain solid tumors including neuroblastoma and some hematological malignancies remain refractory to current treatments. Five-year survival rates for these diseases remain poor (<20-50%) despite the last-resort treatment of Hematopoietic Cell Transplantation (HCT). Hence, there is a clear medical need to develop novel therapies that improve survival.
Umbilical Cord Blood (UCB) is readily available as a HCT donor cell source and has been shown to provide the best disease control in hematological malignancies. Donor immune reconstitution following UCB HCT is rapid and this donor cell source lends itself therefore to facilitating specific donor cell derived, tumor-targeted immunotherapy. Part of the UCB-unit used for the transplantation is available for additional therapeutic options and this allows us to develop cell-based therapies using the same donor for HCT and additional cell therapy. We are developing a dendritic cell vaccine for refractory AML patients treated with UCB transplantation. Dendritic cells are the central players in the immune system that are instrumental for the elicitation of adaptive (T and B cell) anti-tumor immunity. It is our goal to generate a powerful dendritic cell vaccine for refractory AML and neuroblastoma and to position this additional therapy efficiently in a cord blood cell transplantation setting.

The main aims are:
- Develop and modulate a potent CB-derived dendritic cell vaccine to be applied after HCT.
- Perform extensive immunomonitoring in UCB-HCT patients to better position DC vaccination.
- Determine pharmacokinetic and pharmacodynamic properties of immune-therapeutic compounds (anti-GD2 in neuroblastoma) or HCT conditioning agents (e.g. ATG, busulfan) to increase efficacy and limit toxicity.


Techniques
- cell culture, PCR, cloning, flow cytometry, cytokine measurements, CRISPR-Cas9, functional testing (e.g. ADCC, NK-killing assays, T cell stimulation)
- PK-PD modeling

Duration
6 - 9 months

Contact
Dr. S. Nierkens, s.nierkens@umcutrecht.nl
Dr. JJ. Boelens, j.j.boelens@umcutrecht.nl