口腔癌の免疫療法 : 基礎から臨床へ : レンサ球菌,Toll-like receptor,樹状細胞

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  • Immunotherapy for Oral Cancer:Bench to Bed : Streptococcus, Toll-like Receptor, Dendritic Cell
  • コウクウガン ノ メンエキ リョウホウ : キソ カラ リンショウ エ : レンサ キュウキン Toll-like receptor ジュジョウ サイボウ

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OK-432, a penicillin-killed and lyophilized preparation of a low-virulence strain (Su) of Streptococcus pyogenes (group A), is successfully used as an immunotherapeutic agent in many types of malignancies including head and neck cancer. Recently, we succeeded in isolating the effective molecule (lipoteichoic acid-related molecule OK-PSA) by affinity chromatography of a butanol extract of OK-432 on CNBr-activated sepharose 4B bound TS-2 monoclonal antibody that neutralizes interferon-γ-inducing activity of OK-432. In this review, we described the findings regarding the effect of the OK-432 and OK-PSA in enhancing anti-tumor immunity and the molecular mechanism. Our in vitro and in vivo study demonstrated that OK-PSA induces Th1-type cytokines in human as well as in mice, and elicits anti-tumor effect in tumor-bearing mice. Furthermore, our data indicated that the signaling mediated by Toll-like receptor (TLR) 4/MD-2 was involved in regulating OK-432/OK-PSA-induced anti-tumor immunity. It is suggested that OK-PSA is most responsible molecule for the antitumor effect of OK-432, that TLR4 and MD-2 are certain molecular targets for OK-432 as well as OK-PSA, and that expression of these genes may be useful marker to discriminate between responder and nonresponder to OK-432-based immunotherapy. In addition, OK-432/OK-PSA induced tumor-antigen specific cytotoxic T cells via the maturation of dendritic cells (DCs) which are professional antigenpresenting cells. It has been strongly suggested the possibility that OK-432/OK-PSA may be a useful adjuvant for DC therapy.

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