title: Generation of a cord blood-derived Wilms Tumor 1 dendritic cell vaccine for AML patients treated with allogeneic cord blood transplantation.
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.
authors.affiliation: U-DANCE; Laboratory for Translational Immunology; UMC Utrecht ; Utrecht, The Netherlands.
authors.forename: Colin
authors.initials: C
authors.lastname: de Haar
authors.affiliation: U-DANCE; Laboratory for Translational Immunology; UMC Utrecht ; Utrecht, The Netherlands.
authors.forename: Maud
authors.initials: M
authors.lastname: Plantinga
authors.affiliation: U-DANCE; Laboratory for Translational Immunology; UMC Utrecht ; Utrecht, The Netherlands.
authors.forename: Nina Jg
authors.initials: NJ
authors.lastname: Blokland
authors.affiliation: U-DANCE; Laboratory for Translational Immunology; UMC Utrecht ; Utrecht, The Netherlands.
authors.forename: Niek P
authors.initials: NP
authors.lastname: van Til
authors.affiliation: U-DANCE; Laboratory for Translational Immunology; UMC Utrecht ; Utrecht, The Netherlands.
authors.forename: Thijs Wh
authors.initials: TW
authors.lastname: Flinsenberg
authors.affiliation: Laboratory of Experimental Hematology; Tumor Immunology Group (TIGR); Vaccine & Infectious Disease Institute; University of Antwerp ; Wilrijk, Antwerp, Belgium.
authors.forename: Viggo F
authors.initials: VF
authors.lastname: Van Tendeloo
authors.affiliation: Center for Oncological Research (CORE); University of Antwerp ; Wilrijk, Antwerp, Belgium ; Center for Cell Therapy and Regenerative Medicine; Antwerp University Hospital ; Wilrijk, Belgium.
authors.forename: Evelien L
authors.initials: EL
authors.lastname: Smits
authors.affiliation: Bioceros B.V. ; Utrecht, The Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.affiliation: U-DANCE; Laboratory for Translational Immunology; UMC Utrecht ; Utrecht, The Netherlands.
authors.forename: Lotte
authors.initials: L
authors.lastname: Spel
authors.affiliation: Clinical Immunology Section; LTI; UMC Utrecht ; Utrecht, The Netherlands.
authors.forename: Marianne
authors.initials: M
authors.lastname: Boes
authors.affiliation: U-DANCE; Laboratory for Translational Immunology; UMC Utrecht ; Utrecht, The Netherlands ; Department Pediatrics; Blood and Marrow Transplantation Program; UMC Utrecht ; Utrecht, The Netherlands.
authors.forename: Jaap Jan
authors.initials: JJ
authors.lastname: Boelens
authors.affiliation: U-DANCE; Laboratory for Translational Immunology; UMC Utrecht ; Utrecht, The Netherlands ; U-DAIR; LTI; UMC Utrecht ; Utrecht, The Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Nierkens
keywords: WT1; cord blood; dendritic cells; transplantation; vaccination