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01.04.2008 | Original Article

Introduction of functional chimeric E/L-selectin by RNA electroporation to target dendritic cells from blood to lymph nodes

verfasst von: Jan Dörrie, Niels Schaft, Ina Müller, Verena Wellner, Tanja Schunder, Jens Hänig, Gertie J. Oostingh, Michael P. Schön, Caroline Robert, Eckhart Kämpgen, Gerold Schuler

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 4/2008

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Abstract

Background

Inefficient migration of dendritic cells (DC) to regional lymph nodes (LN) upon intracutaneous injection is a major obstacle for effective DC vaccination. Intravenous vaccination is unfavorable, because DC cannot migrate directly from the blood into LN.

Methods

To enable human monocyte-derived (mo)DC to enter LN directly from the blood, we manipulated them by RNA electroporation to express a human chimeric E/L-selectin (CD62E/CD62L) protein, which binds to peripheral node addressin expressed on high endothelial venules.

Results

Transfection efficiency exceeded 95%, and high E/L-selectin surface expression was detected for >48 h. E/L-selectin RNA-transfected DC displayed an identical mature DC phenotype as mock-transfected DC. Furthermore, E/L-selectin-transfected DC maintained their normal CCR7-mediated migration capacity, and their ability to prime and expand functional cytotoxic T cells recognizing MelanA. Most importantly, E/L-selectin-RNA-transfected DC gained the capability to attach to and roll on sialyl-Lewis^X in vitro.

Outlook

The presented strategy can be readily translated into the clinic, as it involves no stable genetic manipulation or viral transformation, and allows targeting of a large number of LN.

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Titel: Introduction of functional chimeric E/L-selectin by RNA electroporation to target dendritic cells from blood to lymph nodes
verfasst von: Jan Dörrie
Niels Schaft
Ina Müller
Verena Wellner
Tanja Schunder
Jens Hänig
Gertie J. Oostingh
Michael P. Schön
Caroline Robert
Eckhart Kämpgen
Gerold Schuler
Publikationsdatum: 01.04.2008
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 4/2008
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-007-0385-1

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Introduction of functional chimeric E/L-selectin by RNA electroporation to target dendritic cells from blood to lymph nodes