This Article Full Text Full Text (PDF) All Versions of this Article: 0008-5472.CAN-08-3920v1 69/7/2927    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Schuurhuis, D. H. Articles by de Vries, I. J. M. Search for Related Content PubMed PubMed Citation Articles by Schuurhuis, D. H. Articles by de Vries, I. J. M.

In situ Expression of Tumor Antigens by Messenger RNA–Electroporated Dendritic Cells in Lymph Nodes of Melanoma Patients

Departments of ¹ Tumor Immunology, ² Medical Oncology, ³ Dermatology, ⁴ Pathology, ⁵ Surgery, ⁶ Nuclear Medicine, and ⁷ Pediatric Hemato-Oncology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands

Requests for reprints: I. Jolanda M. de Vries, Department of Tumor Immunology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands. Phone: 31-24-3617600; Fax: 31-24-3540339; E-mail: j.devries{at}ncmls.ru.nl.

Key Words: dendritic cells • mRNA • expression • migration • immune activation • immunotherapy

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. [Cancer Res 2009;69(7):2927–34]