Generation of a cord blood-derived Wilms Tumor 1 dendritic cell vaccine for AML patients treated with allogeneic cord blood transplantation

Colin de Haar, Maud Plantinga, Nina J G Blokland, Niek P. van Til, Thijs W H Flinsenberg, Viggo F. Van Tendeloo, Evelien L. Smits, Louis Boon, Lotte Spel, Marianne Boes, Jaap Jan Boelens, Stefan Nierkens*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The poor survival rates of refractory/relapsed acute myeloid leukemia (AML) patients after haematopoietic cell transplantation (HCT) requires the development of additional immune therapeutic strategies. As the elicitation of tumor-antigen specific cytotoxic T lymphocytes (CTLs) is associated with reduced relapses and enhanced survival, enhanced priming of these CTLs using an anti-AML vaccine may result in long-term immunity against AML. Cord blood (CB), as allogeneic HCT source, may provide a unique setting for such post-HCT vaccination, considering its enhanced graft-versus-leukemia (GvL) effects and population of highly responsive naïve T cells. It is our goal to develop a powerful and safe immune therapeutic strategy composed of CB-HCT followed by vaccination with CB CD34+-derived dendritic cells (DCs) presenting the oncoprotein Wilms Tumor-1 (WT1), which is expressed in AML-blasts in the majority of patients. Here, we describe the optimization of a clinically applicable DC culture protocol. This two-step protocol consisting of an expansion phase followed by the differentiation toward DCs, enables us to generate sufficient cord blood-derived DCs (CBDCs) in the clinical setting. At the end of the culture, the CBDCs exhibit a mature surface phenotype, are able to migrate, express tumor antigen (WT1) after electroporation with mRNA encoding the full-length WT1 protein, and stimulate WT1-specific T cells.

Original languageEnglish
Pages (from-to)e1023973
Number of pages11
JournalOncoImmunology
Volume4
Issue number11
DOIs
Publication statusPublished - Nov 2015

Keywords

  • cord blood
  • dendritic cells
  • transplantation
  • vaccination
  • WT1

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