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

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

22 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)1-11
Aantal pagina's11
TijdschriftOncoImmunology
Volume4
Nummer van het tijdschrift11
DOI's
StatusGepubliceerd - 2 nov. 2015
Extern gepubliceerdJa

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