Lipoteichoic acid : Augmentation of the therapeutic effect of radiation and 5-fluorouracil in head and neck cancer

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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.