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[Cancer Research 63, 8962-8967, December 15, 2003]
© 2003 American Association for Cancer Research


Regular Articles

Intratumoral Immunization with Tumor RNA-Pulsed Dendritic Cells Confers Antitumor Immunity in a C57BL/6 Pancreatic Murine Tumor Model

Tanja Schmidt1, Carsten Ziske1, Angela Märten1, Stefan Endres3, Klaus Tiemann2, Volker Schmitz1, Marcus Gorschlüter1, Christof Schneider1, Tilman Sauerbruch1 and Ingo G. H. Schmidt-Wolf1

1 Medizinische Klinik und Poliklinik I, Rheinische Friedrich-Wilhelms-Universität, Bonn;
2 Medizinische Klinik und Poliklinik II, Rheinische Friedrich-Wilhelms-Universität, Bonn; and
3 Abteilung für Klinische Pharmakologie, Medizinische Klinik Innenstadt, Klinikum der Universität München, Germany

Pancreatic tumors lack adequate recruitment of immunocompetent cells, especially dendritic cells (DCs). We have shown previously that coculturing of natural killer-like T cells with DCs transfected with pancreatic tumor cell line-derived RNA reverses pancreatic carcinoma cell resistance by directly triggering natural killer-like T lymphocytes in vitro. In the present study, we tested triggering of specific T lymphocytes in vivo by using an immunocompetent mouse strain (C57BL/6).

Syngenic, bone marrow-derived DCs were pulsed with tumor RNA derived from the pancreatic cell line PANC02. This cell line is a ductal pancreatic adenocarcinoma and shows high resistance to every known class of clinically active antitumor agent. PANC02 cells were implanted orthotopically via ultrasound guidance and led to pancreatic tumor formation in all of the mice. Thereafter, tumor RNA-pulsed DCs were injected intratumorally.

Intratumoral administration of tumor RNA-pulsed DCs induced significantly more potent protective immunity than s.c. or i.v. administration. It was significantly more effective than administration with unpulsed DCs or DCs pulsed with a control tumor RNA derived from a lymphomatous cell line (EL4). The antitumor effect was caused by induction of antigen-specific T lymphocytes as shown by additional in vitro studies.

These results favor intratumoral injection of tumor RNA-pulsed DCs for immunotherapy of pancreatic cancer.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2003 by the American Association for Cancer Research.