Clinical grade production of Wilms’ tumor-1 loaded cord blood-derived dendritic cells to prevent relapse in pediatric AML after cord blood transplantation Journal Article


Authors: Plantinga, M.; Lo Presti, V.; de Haar, C. G.; Dünnebach, E.; Madrigal, A.; Lindemans, C. A.; Boelens, J. J.; Nierkens, S.
Article Title: Clinical grade production of Wilms’ tumor-1 loaded cord blood-derived dendritic cells to prevent relapse in pediatric AML after cord blood transplantation
Abstract: Hematopoietic cell transplantation (HCT) is a last resort, potentially curative treatment option for pediatric patients with refractory acute myeloid leukemia (AML). Cord blood transplantation (CBT) results in less relapses and less graft-versus-host disease when compared to other sources. Nevertheless, still more than half of the children die from relapses. We therefore designed a strategy to prevent relapses by inducing anti-AML immunity after CBT, using a CB-derived dendritic cell (CBDC) vaccine generated from CD34+ CB cells from the same graft. We here describe the optimization and validation of good manufacturing practice (GMP)-grade production of the CBDC vaccine. We show the feasibility of expanding low amounts of CD34+ cells in a closed bag system to sufficient DCs per patient for at least three rounds of vaccinations. The CBDCs showed upregulated costimulatory molecules after maturation and showed enhanced CCR7-dependent migration toward CCL19 in a trans-well migrations assay. CBDCs expressed Wilms’ tumor 1 (WT1) protein after electroporation with WT1-mRNA, but were not as potent as CBDCs loaded with synthetic long peptides (peptivator). The WT1-peptivator loaded CBDCs were able to stimulate T-cells both in a mixed lymphocyte reaction as well as in an antigen-specific (autologous) setting. The autologous stimulated T-cells lysed not only the WT1+ cell line, but most importantly, also primary pediatric AML cells. Altogether, we provide a GMP-protocol of a highly mature CBDC vaccine, loaded with WT1 peptivator and able to stimulate autologous T-cells in an antigen-specific manner. Finally, these T-cells lysed primary pediatric AML demonstrating the competence of the CBDC vaccine strategy. © Copyright © 2020 Plantinga, Lo Presti, de Haar, Dünnebach, Madrigal, Lindemans, Boelens and Nierkens.
Keywords: transplantation; dendritic cells; cord blood; immunotherapy; vaccine; good manufacturing practice
Journal Title: Frontiers in Immunology
Volume: 11
ISSN: 1664-3224
Publisher: Frontiers Media S.A.  
Date Published: 2020-09-25
Start Page: 559152
Language: English
DOI: 10.3389/fimmu.2020.559152
PROVIDER: scopus
PMCID: PMC7546401
PUBMED: 33101274
DOI/URL:
Notes: Article -- Export Date: 2 November 2020 -- Source: Scopus
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  1. Jaap Jan Boelens
    216 Boelens