YURA Yoshiaki The University of Tokushima, School of Dentistry, Hospital, Instructor, 歯学部・附属病院, 講師 (00136277)
YOSHIDA Hideo The University of Tokushima, School of Dentistry, Associate Professor, 歯学部, 助教授 (30116131)
1. Interferon (IFN-γ-inducing molecule (OK-LTA) has been purified from the streptococcal agent OK-432, by an affinity chromatography on CNBr-activated Sepharose 4B bound the TS-2 monoclonal antibody which neutralizes IFN-γ-inducing activity of OK-432. The OK-LTA is a glyco-conjugate with a certain structure of lipoteichoic acids. OK-LTA carried striking antitumor activity in vivo and in vitro.
2. OK-LTA induced several cytokines such as IFN-α,-β,-γ, tumor necrosis factor(TNF)-α,-β, interleukin(IL)-2, IL-6, IL-12, IL-18, as well as natural killer(NK) and lymphokine-activated killer(LAK) activities on human peripheral blood mononuclear cells(PBMC).
3. Nude mice bearing human head and neck cancer cells were treated with X-ray(10Gy), 5-FU(40mg/Kg), and/or OK-LTA. It was sugested that the anti-tumor effect of 5-FU were enhanced by OK-LTA.
4. The negative liposome kit (egg lecithin : dicethyphosphate : cholesterol = 7 : 2 : 1, molar ratio) was used to improve the delivery of the agent (OK-LTA) to effector cells and to increase its therapeutic effect. The significantly lesser amounts of OK-LTA encapsulated into liposomes (Lipo-OK-LTA) than OK-LTA alone (1/100 or less amounts of OK-LTA alone) were required to induce IFN-γ, TNF-α,-β, IL-1β, NK, and LAK activities by human PBMC as well as by mouse spleen cells (MSC). Furthermore, higher levels of these activities were detected in PBMC and MSC treated with Lipo-OK-LTA than with OK-LTA alone.
5. All of these activities induced by Lipo-OK-LTA were almost completely neutralized by anti-asialo-GM1 antibody and complement (P<0.001). In in vivo experiments, it was clearly indicated that Lipo-OK-LTA significantly accelerated anti-tumor ability of X-ray and 5-FU.