Development of the therapy with an intratumoral administration of dendritic cells in combination with radiation or anti-cancer drugs against oral cancer : Application to clinical trial.

树突状细胞瘤内给药联合放射或抗癌药物治疗口腔癌的疗法的开发：应用于临床试验。

• 批准号: 16592006
• 负责人: YOSHIDA Hideo
• 金额: $ 2.3万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16592006/
• 关键词: Cancer Immunotherapy; dendritic cell; OK-432; TS-1; Toll-loke receptor; lipoteichoic acid-related molecule OK-PSA; clinical trial; 細胞免疫療法; OK-432; Toll-like receptor 4 (TLR4)

Dendritic cells (DCs) are professional antigen-presenting cells. Adequately matured DCs can stimulate T cells to induce tumor-specific cytotoxic T lymphocytes (CTLs). A streptococcal anticancer immunotherapeutic agent OK-432 can strongly mature DCs. In tumor-bearing mouse model, radiation therapy (RT) or oral administration of anticancer drug TS-1 followed by an intratumoral injection of syngeneic bone-marrow-derived DCs and of OK-432 resulted in inducing CTLs and in inhibiting tumor growth. The therapy did not elicit any significant effects in tumor-bearing mice in which Toll-like receptor (TLR) 4 is mutated. We have already succeeded in isolating an active component of OK-432 (lipoteichoic acid-related molecule OK-PSA). OK-PSA matured DCs far better, than original OK-432 in vitro, and OK-PSA-treated DCs stimulated allogeneic T cells to produce IFN-γ, and to induce allo-antigen specific CTLs. In in vivo model, TS-1+DCs+OK-PSA therapy exhibited anticancer effect stronger than the therapy using TS-1, DCs and OK-432. Based on these basic data, we have started an early stage clinical trial, "the therapy with an intratumoral administration of DCs in combination with TS-1 and OK-432", in oral cancer patients in which the standard therapies were not effective. Of 5 cases, complete remission (CR) was observed in one case, partial remission (PR) in 3 cases, and stable desease (SD) in one case. No significant toxicity over grade 3 was observed. It was strongly suggested that an intratumoral administration in combination with TS-1 and OK-432 is safety and effective in oral cancer patients.

树突状细胞 (DC) 是专业的抗原呈递细胞，充分成熟的 DC 可以刺激 T 细胞诱导肿瘤特异性细胞毒性 T 淋巴细胞 (CTL)，链球菌抗癌免疫治疗剂 OK-432 可以在荷瘤小鼠模型中使 DC 成熟。 、放射治疗 (RT) 或口服抗癌药物 TS-1，然后瘤内注射同基因骨髓来源的 DC 和OK-432 能够诱导 CTL 并抑制肿瘤生长，该疗法对 Toll 样受体 (TLR) 4 突变的荷瘤小鼠没有产生任何显着效果。我们已经成功分离出 OK 的活性成分。 -432（脂磷壁酸相关分子 OK-PSA），OK-PSA 在体外比原始 OK-432 更能促进 DC 成熟，并且 OK-PSA 处理的 DC 刺激同种异体 T。在体内模型中，TS-1+DCs+OK-PSA疗法显示出比使用TS-1、DCs和OK-432的疗法更强的抗癌效果。基于这些基础数据，我们已经在标准疗法无效的口腔癌患者中开始了一项早期临床试验，“瘤内给予DC与TS-1和OK-432组合的疗法”。 5例，完全缓解（CR）1例，强部分缓解（PR）3例，疾病稳定（SD）1例，未观察到3级以上的明显毒性。与 TS-1 和 OK-432 联合治疗口腔癌患者安全有效。

项目成果

Overexpression of iNOS gene suppresses the tumorigenicity and metastasis of oral cancer cells.

• 发表时间: 2004-07
• 期刊: In vivo
• 影响因子: 2.3
• 作者: K. Harada;Supriatno;Shin-ichi Kawaguchi;Onoue Tomitaro;H. Yoshida;Mitsunobu Sato

Chemical Constituents from Fruits and Seeds of Myrica rubra (Myricaceae)

• 发表时间: 2005-04
• 作者: A. Suga;Y. Takaishi;Hiroyuki Nakagawa;Tadashi Iwasa;Mitsunobu Sato;M. Okamoto

OK-432(ピシバニール)の樹状細胞に対する作用

OK-432（Picibanil）对树突状细胞的影响

• 发表时间: 2005
• 期刊: 細胞 37・7
• 作者: 両馬良樹

OK-432由来DNAの抗腫瘍活性

OK-432 衍生 DNA 的抗肿瘤活性

• 发表时间: 2005
• 期刊: 癌と化学療法 31・11
• 作者: 押川哲也

Acquisition of lymph node, but not distant metastatic potentials, by the overexpression of CXCR4 in human oral squamour cell carcinoma

通过人口腔鳞状细胞癌中 CXCR4 的过表达获得淋巴结，但不获得远处转移潜能

• 发表时间: 2004
• 期刊: Lab Invest 84・12
• 作者: T.Wakira;M.Mogi;K.Kurita;M.Kuzushima;A.Togari;Masato Okamoto;小俣裕昭 他4名;押川哲也;Hiroyuki Nakagawa;Wakita et al.;小俣裕昭 他4名;Koji Harada;Sharif Uddin Ahmed;田野智之;Koji Harada;Hiroaki Omata;両馬良樹;Hiroaki Omata;Koji Harada;Hiroaki Omata;Masato Okamoto;Supriatno;Sharif Uddin Ahmed;Masato Okamoto;Daisuke Uchida;Masato Okamoto;Daisuke Uchida
• 通讯作者: Daisuke Uchida