[Anti-tumor effect of intratumoral administration of dendritic cells in combination with TS-1 and OK-432].
We investigated the in vivo anti-tumor effect of intratumoral administration of dendritic cells (DCs) after chemotherapy using TS-1, and followed by immunopotentiator OK-432. Both in Meth-A-bearing BALB/c and in SCCV II-bearing C3H/HeN mice, one week of oral administration of TS-1 affected a partial eradication of established tumors. TS-1 followed by DCs and OK-432 resulted in a marked inhibition in tumor growth, and also contributed to a greater prolongation of survival. Cytotoxic activities of tumor-infiltrating lymphocytes and draining lymph node cells against inoculated tumor cells were significantly increased by the therapy. Cytotoxic memory T cells were also induced. The same therapy was also applied to SCCV II-bearing C3H/HeJ mice in which the Toll-like receptor (TLR) 4 is mutated; no immunotherapeutic effect was observed in the mice. These findings suggest that local DC therapy in combination with TS-1 and OK-432 may well be a useful strategy for the treatment of solid tumors, and that TLR4 signaling is involved in the success of this therapy.
Okamoto
Masato
M
Second Dept. of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry.
Ahmed
Sharif Uddin
SU
Oshikawa
Tetsuya
T
Tano
Tomoyuki
T
Sato
Mitsunobu
M
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D003713:Dendritic Cells / Q000637:transplantation*; D004338:Drug Combinations; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000628:therapy*; D010094:Oxonic Acid / Q000008:administration & dosage*; D010844:Picibanil / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D011956:Receptors, Cell Surface / Q000502:physiology; D012513:Sarcoma, Experimental / Q000628:therapy; D005641:Tegafur / Q000008:administration & dosage*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D004338:Drug Combinations; D008562:Membrane Glycoproteins; D011725:Pyridines; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; C079198:S 1 (combination); D005641:Tegafur; D010844:Picibanil; D010094:Oxonic Acid