Intratumoral immunization with tumor RNA-pulsed dendritic cells confers antitumor immunity in a C57BL/6 pancreatic murine tumor model.
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.
Schmidt
Tanja
T
Medizinische Klinik und Poliklinik I, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany.
Ziske
Carsten
C
Märten
Angela
A
Endres
Stefan
S
Tiemann
Klaus
K
Schmitz
Volker
V
Gorschlüter
Marcus
M
Schneider
Christof
C
Sauerbruch
Tilman
T
Schmidt-Wolf
Ingo G H
IG
D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000276:immunology* / Q000628:therapy*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D016219:Immunotherapy, Adoptive / Q000379:methods*; D015552:Injections, Intralesional; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy*; D012334:RNA, Neoplasm / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D012334:RNA, Neoplasm