title: In situ expression of tumor antigens by messenger RNA-electroporated dendritic cells in lymph nodes of melanoma patients.
abstract: Electroporation of dendritic cells (DC) with mRNA encoding tumor-associated antigens (TAA) for cancer immunotherapy has been proved efficient and clinically safe. It obviates prior knowledge of CTL and Th epitopes in the antigen and leads to the presentation of multiple epitopes for several HLA alleles. Here we studied the migration capacity and the antigen expression of mRNA-electroporated DC (mRNA-DC) in lymph nodes after vaccination in melanoma patients. DC were electroporated with mRNA encoding gp100 or tyrosinase, labeled with indium-111 and superparamagnetic iron oxide particles, and injected intranodally in melanoma patients 24 to 48 hours before scheduled dissection of regional lymph nodes. Immunohistochemical analysis of the lymph nodes after surgery revealed that mRNA-DC migrated from the injection site into the T-cell areas of the same and subsequent lymph nodes, where they expressed the antigen encoded by the electroporated mRNA. Furthermore, vaccine-related CD8(+) T-cell responses could be detected in 7 of 11 patients vaccinated with mRNA-DC. Together these data show that mature DC electroporated with mRNA encoding TAA migrate and express antigens in the lymph nodes and induce specific immune responses.
authors.affiliation: Department of Tumor Immunology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
authors.forename: Danita H
authors.initials: DH
authors.lastname: Schuurhuis
authors.forename: Pauline
authors.initials: P
authors.lastname: Verdijk
authors.forename: Gerty
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authors.lastname: Schreibelt
authors.forename: Erik H J G
authors.initials: EH
authors.lastname: Aarntzen
authors.forename: Nicole
authors.initials: N
authors.lastname: Scharenborg
authors.forename: Annemiek
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authors.lastname: de Boer
authors.forename: Mandy W M M
authors.initials: MW
authors.lastname: van de Rakt
authors.forename: Marieke
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authors.lastname: Kerkhoff
authors.forename: Marie-Jeanne P
authors.initials: MJ
authors.lastname: Gerritsen
authors.forename: Femke
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authors.lastname: Eijckeler
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authors.initials: JJ
authors.lastname: Bonenkamp
authors.forename: Willeke
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authors.lastname: Blokx
authors.forename: J Han
authors.initials: JH
authors.lastname: van Krieken
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authors.initials: WJ
authors.lastname: Oyen
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
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authors.initials: GJ
authors.lastname: Adema
authors.forename: I Jolanda M
authors.initials: IJ
authors.lastname: de Vries