2025/06/09 更新

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写真a

タナカ ヨシヒロ
田中 芳浩
TANAKA YOSHIHIRO
所属
九州大学病院 先端分子・細胞治療科 助教
医学部 医学科(併任)
職名
助教
連絡先
メールアドレス
電話番号
0926425102
プロフィール
特定細胞加工物製造施設(分子・細胞調製センター(MCPC))の施設管理・運営
外部リンク

論文

  • A phase I clinical trial of RNF43 peptide-related immune cell therapy combined with low-dose cyclophosphamide in patients with advanced solid tumors. 査読 国際誌

    Hijikata Y, Okazaki T, Tanaka Y, Murahashi M, Yamada Y, Yamada K, Takahashi A, Inoue H, Kishimoto J, Nakanishi Y, Oda Y, Nakamura Y, Tani K.

    PLoS One   13 ( 1 )   1 - 21   2018年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The objective of this study was to investigate the safety and the tolerability of combined cellular immunotherapy with low-dose cyclophosphamide (CPA) in patients with advanced solid tumors. This study targeted a novel tumor-associated antigen, ring finger protein 43 (RNF43). Eligible patients were resistant to standard therapy, HLA-A*24:02- or A*02:01-positive and exhibiting high RNF43 expression in their tumor cells. They were administered 300 mg/m2 CPA followed by autologous lymphocytes, preliminarily cultured with autologous RNF43 peptide-pulsed dendritic cells (DCs), RNF43 peptide-pulsed DCs and systemic low dose interleukin-2. The primary endpoint was safety whereas the secondary endpoint was immunological and clinical response to treatment. Ten patients, in total, were enrolled in this trial. Primarily, no adverse events greater than Grade 3 were observed. Six out of 10 patients showed stable disease (SD) on day 49, while 4 other patients showed progressive disease. In addition, one patient with SD exhibited a partial response after the second trial. The frequency of regulatory T cells (Tregs) in patients with SD significantly decreased after CPA administration. The ratio of interferon-γ-producing, tumor-reactive CD8+ T cells increased with time in patients with SD. We successfully showed that the combination of immune cell therapy and CPA was safe, might induce tumor-specific immune responses and clinical efficacy, and was accompanied by a decreased ratio of Tregs in patients with RNF43-positive advanced solid tumors.

    DOI: 10.1371/journal.pone.0187878

  • Phase I clinical trial of a five-peptide cancer vaccine combined with cyclophosphamide in advanced solid tumors. 査読 国際誌

    Murahashi M, Hijikata Y, Yamada K, Tanaka Y, Kishimoto J, Inoue H, Marumoto T, Takahashi A, Okazaki T, Takeda K, Hirakawa M, Fujii H, Okano S, Morita M, Baba E, Mizumoto K, Maehara Y, Tanaka M, Akashi K, Nakanishi Y, Yoshida K, Tsunoda T, Tamura K, Nakamura Y, Tani K.

    Clinical Immunology   166 ( 48 )   48 - 58   2016年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We designed a phase I trial to investigate the safety, immune responses and clinical benefits of a five-peptide cancer vaccine in combination with chemotherapy. Study subjects were patients positive for HLA-A2402 with locally advanced, metastatic, and/or recurrent gastrointestinal, lung or cervical cancer. Eighteen patients including nine cases of colorectal cancer were treated with escalating doses of cyclophosphamide 4 days before vaccination. Five HLA-A2402-restricted, tumor-associated antigen (TAA) epitope peptides from KOC1, TTK, URLC10, DEPDC1 and MPHOSPH1 were injected weekly for 4 weeks. Treatment was well tolerated without any adverse events above grade 3. Analysis of peripheral blood lymphocytes showed that the number of regulatory T cells dropped from baseline after administration of cyclophosphamide and confirmed that TAA-specific T cell responses were associated significantly with longer overall survival. This phase I clinical trial demonstrated safety and promising immune responses that correlated with vaccine-induced T-cell responses. Therefore, this approach warrants further clinical studies.

    DOI: 10.1016/j.clim.2016.03.015

  • TLR7 ligand augments GM-CSF-initiated antitumor immunity through activation of plasmacytoid dendritic cells. 査読 国際誌

    Narusawa M, Inoue H, Sakomoto C, Matsumura Y, Takahashi A, Inoue T, Watanabe A, Miyamoto S, Miura Y, Hijikata Y, Tanaka Y, Inoue M, Takayama K, Okazaki T, Hasagawa M, Nakanishi Y, Tani K.

    Cancer Immunol Res.   2 ( 6 )   568 - 580   2014年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    TLR7 ligand augments GM-CSF-initialed antitumor immunity through activation of plasmacytoid dendritic cells.Vaccination with irradiated granulocyte macrophage colony-stimulating factor (GM-CSF)-transduced autologous tumor cells (GVAX) has been shown to induce therapeutic antitumor immunity. However, its effectiveness is limited. We therefore attempted to improve the antitumor effect by identifying little-known key pathways in GM-CSF-sensitized dendritic cells (GM-DC) in tumor-draining lymph nodes (TDLN). We initially confirmed that syngeneic mice subcutaneously injected with poorly immunogenic Lewis lung carcinoma (LLC) cells transduced with Sendai virus encoding GM-CSF (LLC/SeV/GM) remarkably rejected the tumor growth. Using cDNA microarrays, we found that expression levels of type I interferon (IFN)-related genes, predominantly expressed in plasmacytoid DCs (pDC), were significantly upregulated in TDLN-derived GM-DCs and focused on pDCs. Indeed, mouse experiments demonstrated that the effective induction of GM-CSF-induced antitumor immunity observed in immunocompetent mice treated with LLC/SeV/GM cells was significantly attenuated when pDC-depleted or IFNα receptor knockout (IFNAR(-/-)) mice were used. Importantly, in both LLC and CT26 colon cancer-bearing mice, the combinational use of imiquimod with autologous GVAX therapy overcame the refractoriness to GVAX monotherapy accompanied by tolerability. Mechanistically, mice treated with the combined vaccination displayed increased expression levels of CD86, CD9, and Siglec-H, which correlate with an antitumor phenotype, in pDCs, but decreased the ratio of CD4(+)CD25(+)FoxP3(+) regulatory T cells in TDLNs. Collectively, these findings indicate that the additional use of imiquimod to activate pDCs with type I IFN production, as a positive regulator of T-cell priming, could enhance the immunologic antitumor effects of GVAX therapy, shedding promising light on the understanding and treatment of GM-CSF-based cancer immunotherapy.

    DOI: 10.1158/2326-6066.CIR-13-0143

  • 固形腫瘍に対する新規免疫療法の開発―当科における第I相臨床試験の現状― 査読

    土方 康基, 村橋(伊賀) 睦了, 岡崎 利彦, 田中 芳浩, 大平 公亮, 岡野 慎士, 久野 晃聖, 高橋 淳, 丸本 朋稔, 井上 博之, 谷 憲三朗

    臨床血液   53 ( 5 )   487 - 492   2012年6月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.11406/rinketsu.53.487

  • 抗腫瘍免疫療法における新戦略-New strategies of immunetherapy targeting malignancy- 査読

    村橋(伊賀)睦了, 土方 康基, 末廣 陽子, 田中 芳浩, 下田 真也, 丸本 朋稔, 岡崎 利彦, 吉田浩二, 角田 卓也, 谷 憲三朗.

    臨床血液   51 ( 11 )   1654 - 1660   2010年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.11406/rinketsu.51.1654

  • Remarkably high inhibitory effects of docosahexaenoic acid incorporated into hybrid liposomes on the growth of tumor cells along with apoptosis. 査読 国際誌

    Tanaka Y, Goto K, Matsumoto Y, Ueoka R.

    International Journal of Pharmaceutics   359 ( 1-2 )   264 - 271   2008年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Inhibitory effects of hybrid liposomes composed of l-alpha-dimyristoylphosphatidylcholine (DMPC) and polyoxyethylene (20) sorbitan monooleate (Tween 80) including polyunsaturated fatty acids or their ethyl esters (HL-PUFA) on the growth of human tumor cells were examined in vitro. Remarkably high inhibitory effects of HL including docosahexaenoic acid (HL-DHA) and alpha-linolenic acid ethyl ester (HL-ALAE) on the growth of lung carcinoma (RERF-LC-OK and A549) cells, colon tumor (WiDr) cells and stomach tumor (MKN45) cells were obtained. The addition of vitamin E (alpha-tocopherol) to HL-DHA and -ALAE prevented almost completely the growth inhibition of A549 cells distinct from the other tumor cells used in this study. On the other hand, fluorescence microscopic and flow cytometric analyses indicated that the inhibitory effects of HL-DHA on the growth of RERF-LC-OK, WiDr and MKN45 cells could be attained through the induction of apoptosis.

    DOI: 10.1016/j.ijpharm.2008.03.045.

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所属学協会

  • 再生医療学会

共同研究・競争的資金等の研究課題

  • 医療技術実用化総合促進事業

    2018年4月 - 2019年3月

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    担当区分:研究分担者 

特筆しておきたい臨床活動

  • 保険診療に使用する再生医療等製品の製造・品質業務を継続的に実施する。