レンサ球菌由来リポタイコ酸関連分子の抗腫瘍免疫活性の解析とその口腔癌治療への応用に関する研究

DOI Web Site 参考文献24件
  • 岡本 正人
    武蔵野大学薬学部薬学研究所薬物療法学研究室

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タイトル別名
  • Anti-cancer immunity of a lipoteichoic acid-related molecule derived from Streptococcus and its application to oral cancer therapy
  • シュクダイ ホウコク レンサ キュウキン ユライ リポタイコサン カンレン ブンシ ノ コウシュヨウ メンエキ カッセイ ノ カイセキ ト ソノ コウクウ ガン チリョウ エノ オウヨウ ニ カンスル ケンキュウ

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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 oral 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 the interferon-γ-inducing activity of OK-432. In this review, we describe the findings regarding the effect of 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 induced Thl-type cytokines in humans as well as in mice, and elicited antitumor 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 antitumor immunity. It is suggested that OK-PSA is the molecule most responsible 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 a useful marker to discriminate between responders and nonresponders to OK-432-based immunotherapy. In addition, OK-432/OK-PSA induced tumorantigen specific cytotoxic T cells via the maturation of dendritic cells (DCs) which are professional antigenpresenting cells. It is strongly suggested that OK-432/OK-PSA may be a useful adjuvant for DC therapy.

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