[Experimental study for a combination chemo-immunotherapy using dendritic cells].
This study was designed to seek for the optimal anticancer agents for a combination of chemotherapy and specific immunotherapy using dendritic cells (DC) in gastric cancer. We investigated the immuno-suppressive activity of anticancer agents on human peripheral blood mononuclear cells (PBMC), apoptosis inducing activity on gastric cancer cells and expression of Toll-like receptor (TLR)-4 mRNA on immatureDCs (iDCs) by paclitaxel (TXL) and docetaxel (TXT). We further compared the cytotoxicity of cytotixic T lymphocytes (CTLs) induced by DCs pulsed with tumor cell lysate and apoptotic cells induced by TXT. Although most of the anticancer agents demonstrated the suppression activity on proliferation of PBMC in a dose dependent manner, TXT, doxifluridine and irinotecan did not show the suppressive activity on PBMC even in the highest drug concentration. About 60% of gastric cancer cells demonstrated apoptosis after a 24-48 hour treatment with both TXL and TXT. Expression of TLR-4 mRNA in iDCs was up-regulated by TXT, not by TXL, and peaked at 2 hours after the treatment. CTLs induced by DCs pulsed with tumor cell lysate and apoptotic cells showed a similar killing activity to target cells. These results suggest that TXT appears to be an optimal anticancer agent for a combination therapy with chemotherapy and tumor specific immunotherapy using dendritic cells in gastric cancer.
Kashimura
Seigo
S
First Dept. of Surgery, Fukushima Medical University.
Terashima
Masanori
M
Soeta
Nobutoshi
N
Otani
Satoshi
S
Hoshino
Mika
M
Kanzaki
Norio
N
Matsuyama
Shinichi
S
Hoshino
Yutaka
Y
Kogure
Michihiko
M
Gotoh
Mitsukazu
M
Ogata
Takashi
T
Ohto
Hitoshi
H
D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D017209:Apoptosis / Q000502:physiology; D003713:Dendritic Cells / Q000637:transplantation*; D000077143:Docetaxel; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000032:analysis; D017239:Paclitaxel / Q000008:administration & dosage*; D011956:Receptors, Cell Surface / Q000032:analysis; D013274:Stomach Neoplasms / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D043823:Taxoids / Q000008:administration & dosage*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D043823:Taxoids; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D000077143:Docetaxel; D017239:Paclitaxel