Resistance of pancreatic carcinoma cells is reversed by coculturing NK-like T cells with dendritic cells pulsed with tumor-derived RNA and CA 19-9.
Immunization with defined tumor antigens is limited to the small number of cancers in which specific tumor antigens have been defined but insufficient tumor material is available to produce an antitumor vaccine. In this study, we investigated whether pulsing dendritic cells (DC) using a liposomal transfer technique with a pancreatic tumor cell line-derived RNA can effectively activate NK-like T cells and tumor immunity. Pulsed DC were cocultured with NK-like T cells, i.e., CD3+CD56+ cells, as immunologic effector cells. Target cells resistant to NK-like T-cell-mediated lysis were used. Total tumor-derived RNA transfected into DC was found to completely reverse tumor cell resistance. Total tumor RNA transfection (30 microg) was found to be superior to poly(A)(+) RNA transfection (5 microg) in inducing NK-like T lymphocytes. Interestingly, additional pulsing of DC with the CA 19-9 peptide in a CA 19-9-positive cell line further increased the sensitivity of pancreas carcinoma cells to NK-like T cells. Treatment of tumor RNA with RNase completely blocked the effect of RNA-transfected DC on NK-like T cells, suggesting that intact tumor-derived RNA is needed for reversal of tumor cell resistance. In conclusion, coculture of NK-like T cells with DC transfected with pancreatic tumor cell line-derived RNA reverses pancreatic tumor cell resistance by directly triggering NK-like T lymphocytes.
Ziske
C
C
Medizinische Klinik und Poliklinik I, Rheinische Friedrich-Wilhelms-Universität, Bonn, 53105, Germany.
Märten
A
A
Schöttker
B
B
Buttgereit
P
P
Schakowski
F
F
Gorschlüter
M
M
von Rücker
A
A
Scheffold
C
C
Chao
N
N
Sauerbruch
T
T
Schmidt-Wolf
I G
IG
D018395:CA-19-9 Antigen / Q000627:therapeutic use*; D017252:CD3 Complex / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D002470:Cell Survival; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D018014:Gene Transfer Techniques; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D008285:Major Histocompatibility Complex; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D011061:Poly A / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D018395:CA-19-9 Antigen; D017252:CD3 Complex; D019002:CD56 Antigen; D008081:Liposomes; D011061:Poly A; D012313:RNA; D007770:L-Lactate Dehydrogenase