Research Experience 【 display / non-display 】

Research Experience 【 display / non-display 】

• 2016.11

  -

  Now

  札幌医科大学 医学部 腫瘍内科学講座  

  講師

• 2011.04

  -

  2016.10

  Sapporo Medical University   School of Medicine   助教

• 2009.03

  -

  2011.03

  Harvard University Dana-Farber Cancer Institute  

  リサーチ フェロー

Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Gastroenterology  

• Life sciences   Hematology and oncology  

• Life sciences   Tumor diagnostics and therapeutics   がんゲノム医療

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University School of Medicine   Department of Medical Oncology  

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• Medical Oncologist

• NASH

• 癌細胞における鉄代謝

• 新規大腸癌治療法開発

• 細胞標的治療

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Papers 【 display / non-display 】

Papers 【 display / non-display 】

• A phase 1 trial of NY-ESO-1-specific TCR-engineered T-cell therapy combined with a lymph node-targeting nanoparticulate peptide vaccine for the treatment of advanced soft tissue sarcoma.

  Mikiya Ishihara, Yoshihiro Nishida, Shigehisa Kitano, Akira Kawai, Daisuke Muraoka, Fumiyasu Momose, Naozumi Harada, Yoshihiro Miyahara, Naohiro Seo, Hiroyoshi Hattori, Kohichi Takada, Makoto Emori, Shigeki Kakunaga, Makoto Endo, Yoshihiro Matsumoto, Tetsuro Sasada, Eiichi Sato, Tomomi Yamada, Akihiko Matsumine, Yasuhiro Nagata, Takashi Watanabe, Shinichi Kageyama, Hiroshi Shiku

  International journal of cancer   152 ( 12 ) 2554 - 2566  2023.06  [International journal]

  　View Summary

  The efficacy of immune checkpoint inhibitors is limited in refractory solid tumors. T-cell receptor gene-modified T (TCR-T)-cell therapy has attracted attention as a new immunotherapy for refractory cold tumors. We first investigated the preclinical efficacy and mode of action of TCR-T cells combined with the pullulan nanogel:long peptide antigen (LPA) vaccine in a mouse sarcoma model that is resistant to immune checkpoint inhibition. Without lymphodepletion, the pullulan nanogel:LPA vaccine markedly increased the number of TCR-T cells in the draining lymph node and tumor tissue. This change was associated with enhanced CXCR3 expression in TCR-T cells in the draining lymph node. In the phase 1 trial, autologous New York esophageal squamous cell carcinoma 1 (NY-ESO-1)-specific TCR-T cells were infused twice into HLA-matched patients with NY-ESO-1+ soft tissue sarcoma (STS). The pullulan nanogel:LPA vaccine contains an epitope recognized by TCR-T cells, and it was subcutaneously injected 1 day before and 7 days after the infusion of TCR-T cells. Lymphodepletion was not performed. Three patients with refractory synovial sarcoma (SS) were treated. Two out of the three patients developed cytokine release syndrome (CRS) with low-to-moderate cytokine level elevation. We found obvious tumor shrinkage lasting for more than 2 years by tumor imaging and long-term persistence of TCR-T cells in one patient. In conclusion, NY-ESO-1-specific TCR-T-cell therapy plus vaccination with the pullulan nanogel carrying an LPA containing the NY-ESO-1 epitope without lymphodepletion is feasible and can induce promising long-lasting therapeutic effects in refractory SS (Registration ID: JMA-IIA00346).

  DOI PubMed

• Assessment for the timing of comprehensive genomic profiling tests in patients with advanced solid cancers.

  Kanako Hagio, Junko Kikuchi, Kohichi Takada, Hiroki Tanabe, Minako Sugiyama, Yoshihito Ohhara, Toraji Amano, Satoshi Yuki, Yoshito Komatsu, Takahiro Osawa, Kanako C Hatanaka, Yutaka Hatanaka, Takashi Mitamura, Ichiro Yabe, Yoshihiro Matsuno, Atsushi Manabe, Akihiro Sakurai, Atsushi Ishiguro, Masato Takahashi, Hiroshi Yokouchi, Hirohito Naruse, Yusuke Mizukami, Hirotoshi Dosaka-Akita, Ichiro Kinoshita

  Cancer science    2023.05  [International journal]

  　View Summary

  Comprehensive genomic profiling (CGP) tests have been covered by public insurance in Japan for patients with advanced solid tumors who have completed or are completing standard treatments or do not have them. Therefore, genotype-matched drug candidates are often unapproved or off-label, and improving clinical trial access is critical, involving the appropriate timing of CGP tests. To address this issue, we analyzed the previous treatment data for 441 patients from an observational study on CGP tests discussed by the expert panel at Hokkaido University Hospital between August 2019 and May 2021. The median number of previous treatment lines was two; three or more lines accounted for 49%. Information on genotype-matched therapies was provided to 277 (63%). Genotype-matched clinical trials were ineligible because of an excess number of previous treatment lines or use of specific agents were found in 66 (15%) patients, with the highest proportion in breast and prostate cancers. Many patients met the exclusion criteria of one to two or more treatment lines across cancer types. In addition, previous use of specific agents was a frequent exclusion criterion for breast, prostate, colorectal, and ovarian cancers. The patients with tumor types with a low median number (two or fewer) of previous treatment lines, including most rare cancers, primary unknown cancers, and pancreatic cancers, had significantly fewer ineligible clinical trials. The earlier timing of CGP tests may improve access to genotype-matched clinical trials, with their proportion varying by cancer type. Each relevant society needs to advocate the desirable timing of CGP testing nationwide.

  DOI PubMed

• Chimeric antigen receptor T-cell therapy targeting a MAGE A4 peptide and HLA-A*02:01 complex for unresectable advanced or recurrent solid cancer: protocol for a multi-institutional phase 1 clinical trial.

  Satoshi Okumura, Mikiya Ishihara, Naomi Kiyota, Kimikazu Yakushijin, Kohichi Takada, Shinichiro Kobayashi, Hiroaki Ikeda, Makoto Endo, Koji Kato, Shigehisa Kitano, Akihiko Matsumine, Yasuhiro Nagata, Shinichi Kageyama, Taizo Shiraishi, Tomomi Yamada, Keizo Horibe, Kazuto Takesako, Hiroshi Miwa, Takashi Watanabe, Yoshihiro Miyahara, Hiroshi Shiku

  BMJ open   12 ( 11 ) e065109  2022.11  [International journal]

  　View Summary

  INTRODUCTION: Adoptive cell transfer of genetically engineered T cells is a promising treatment for malignancies; however, there are few ideal cancer antigens expressed on the cell surface, and the development of chimeric antigen receptor T cells (CAR-T cells) for solid tumour treatment has been slow. CAR-T cells, which recognise major histocompatibility complex and peptide complexes presented on the cell surface, can be used to target not only cell surface antigens but also intracellular antigens. We have developed a CAR-T-cell product that recognises the complex of HLA-A*02:01 and an epitope of the MAGE-A4 antigen equipped with a novel signalling domain of human GITR (investigational product code: MU-MA402C) based on preclinical studies. METHODS AND ANALYSIS: This is a dose-escalation, multi-institutional, phase 1 study to evaluate the tolerability and safety of MU-MA402C for patients with MAGE A4-positive and HLA-A*02:01-positive unresectable advanced or recurrent solid cancer. Two dose cohorts are planned: cohort 1, MU-MA402C 2×108/person; cohort 2, MU-MA402C 2×109/person. Prior to CAR-T-cell infusion, cyclophosphamide (CPA) and fludarabine (FLU) will be administered as preconditioning chemotherapy. Three evaluable subjects per cohort, for a total of 6 subjects (maximum of 12 subjects), will be recruited for this clinical trial. The primary endpoints are safety and tolerability. The severity of each adverse event will be evaluated in accordance with Common Terminology Criteria for Adverse Events V.5.0. The secondary endpoint is efficacy. Antitumour response will be evaluated according to Response Evaluation Criteria in Solid Tumours V.1.1. ETHICS AND DISSEMINATION: This clinical trial will be conducted in accordance with the current version of Good Clinical Practice. The protocol was approved by the Clinical Research Ethics Review Committee of Mie University Hospital (approval number F-2021-017). The trial results will be published in peer-reviewed journals and/or disseminated through international conferences. TRIAL REGISTRATION NUMBER: jRCT2043210077.

  DOI PubMed

• Achievement of a durable response with eribulin for relapsed cardiac metastasis of uterine leiomyosarcoma after surgery: a case report and literature review

  Makoto Usami, Kohichi Takada, Hajime Nakamura, Kazuyuki Murase, Yohei Arihara, Naotaka Hayasaka, Tomohiro Kubo, Koji Miyanishi, Junji Kato, Makoto Emori, Shintaro Sugita

  Annals of Palliative Medicine ( AME Publishing Company )  12 ( 1 ) 205 - 211  2022.10  [Refereed]

  Authorship：   Corresponding author

  DOI

• Effect of comprehensive cancer genomic profiling on therapeutic strategies and clinical outcomes in patients with advanced biliary tract cancer: A prospective multicenter study

  Kohichi Takada, Tomohiro Kubo, Junko Kikuchi, Makoto Yoshida, Ayako Murota, Yohei Arihara, Hajime Nakamura, Hiroyuki Nagashima, Hiroki Tanabe, Shintaro Sugita, Yumi Tanaka, Ayana Miura, Yoshihito Ohhara, Atsushi Ishiguro, Hiroshi Yokouchi, Yasuyuki Kawamoto, Yusuke Mizukami, Hirofumi Ohnishi, Ichiro Kinoshita, Akihiro Sakurai

  Frontiers in Oncology ( Frontiers Media SA )  12  2022.09  [Refereed]

  Authorship：   Lead author  , Corresponding author

  　View Summary

  Characterization of the genomic landscape of biliary tract cancer (BTC) may lead to applying genotype-matched therapy for patients with this disease. Evidence that comprehensive cancer genomic profiling (CGP) guides genotype-matched therapy to improve clinical outcomes is building. However, the significance of CGP in patients with BTC remains unclarified in clinical practice. Therefore, the purposes of this study were to assess the utility of CGP and identify associations between clinical outcomes and genomic alterations in patients with BTC. In this prospective analysis, detection rates for actionable genomic alterations and access rates for genotype-matched therapy were analyzed in 72 patients with advanced BTC who had undergone commercial CGP. Cox regression analyses assessed relationships between overall survival and genomic alterations detected with CGP. The most common genomic alterations detected were TP53 (41, 56.9%), followed by CDKN2A/B (24, 33.3%/20, 27.8%), and KRAS (20, 27.8%). Actionable genomic alterations were identified in 58.3% (42/72) of patients. Detection rates for FGFR2 fusions, IDH1 mutations, and BRAF V600E were low in this cohort. Eight (11.1%) patients received genotype-matched therapy. For patients with intrahepatic cholangiocarcinoma (ICC), CDKN2A/B loss was associated with shorter overall survival. These real-world data demonstrate that CGP can identify therapeutic options in patients with advanced BTC. CDKN2A/B loss was identified as a poor prognostic factor in patients with ICC. Thus, this study provides a rationale for considering CGP in planning therapeutic strategies for advanced BTC.

  DOI

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• 食道癌 診断と治療のup to date 食道腺癌を含めて 切除可能進行食道癌に対する三剤併用療法ベースの化学放射線療法は手術療法を代替できるか?:傾向スコアマッチング分析

  大沼 啓之, 小野山 直輝, 濱口 孝太, 早坂 尚貴, 佐藤 昌則, 村瀬 和幸, 高田 弘一, 宮西 浩嗣, 村上 武志, 伊東 竜哉, 信岡 隆幸, 竹政 伊知朗, 土屋 高旭, 長谷川 智一, 堀 正和, 染谷 正則, 坂田 耕一, 加藤 淳二

  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 ( 日本消化器病学会-北海道支部 )  128回・122回   35 - 35  2021.03

• 再発または遠隔転移を有する口腔癌に対しニボルマブ投与は遺伝子変異が指標となるか

  荻和弘, 小林淳一, 小林淳一, 西山廣陽, 小池和茂, 高田弘一, 染谷正則, 宮崎晃亘

  日本癌治療学会学術集会(Web)   58th  2020

  J-GLOBAL

• 低用量IL2はBCL2の発現を誘導することでCD4制御性T細胞のアポトーシスを抑制する(Low-close interleukin-2 induces BCL2 expression and resistance to apoptosis in CD4 regulatory T Cells)

  松野 鉄平, 村瀬 和幸, 高田 弘一, 河野 豊, 平川 昌宏, 宮西 浩嗣, 小船 雅義, 加藤 淳二

  札幌医学雑誌 ( 札幌医科大学 )  87 ( 1-6 ) 49 - 61  2018.12

  　View Summary

  制御性T細胞(Treg)は自己免疫寛容や恒常性の維持に重要な役割を果たしている。インターロイキン2(IL-2)はTregの増加、活動、生存に非常に重要である。既報では低用量IL-2はTregの増加に選択的に作用し、自己免疫疾患の臨床症状を改善させると報告されている。IL-2がTregの内因性アポトーシスにどのように作用するのかを調べるために、我々はBH3プロファイリングを用い、ミトコンドリアのアポトーシスプライミングを定量的に測定した。BH3ペプチドパターンではTregのプライミングがTconより多く、それがBCL2に依存していることを示した。実際に、TregではTconよりもBCL2の発現が低かった。IL-2の作用を調べるために、TregとTconに分け、異なった用量のIL-2で培養した。Tregでは低用量のIL-2(10 IU/ml)でプライミングは低下しBCL2発現は増加したが、Tconではプライミングの低下とBCL2発現の増加には高用量のIL-2(>100 IU/ml)が必要であった。また、低用量IL-2はTregにおいてのみアポトーシスへの感受性を減らすことがアポトーシスアッセイによって判明した。ABT-199というBCL2選択的阻害剤はTregとTcon両者のプライミングとアポトーシスを増加させる。IL2はTregにおいてのみこのABT-199の効果を打ち消した。このことからTregにおけるIL2による内因性アポトーシスの阻害がBCL2に依存していることが判明した。(著者抄録)

• A multidisciplinary treatment approach using docetaxel, nedaplatin, and 5-FU for advanced esophageal cancer

  Hiroyuki Ohnuma, Masahiro Hirakawa, Shohei Kikuchi, Yasushi Sato, Koichi Takada, Koji Miyanishi, Junji Kato

  ANNALS OF ONCOLOGY ( OXFORD UNIV PRESS )  28  2017.10

  Research paper, summary (international conference)  

• P53-RESTORING SMALL MOLECULE CP-31398 INDUCES APOPTOSIS VIA INDUCTION OF REACTIVE OXIDATIVE SPECIES IN HUMAN MULTIPLE MYELOMA

  Y. Arihara, K. Takada, Y. Kawano, N. Hayasaka, H. Nakamura, S. Kikuchi, Y. Kamihara, K. Murase, H. Ikeda, S. Iyama, T. Sato, K. Miyanishi, M. Kobune, J. Kato

  HAEMATOLOGICA ( FERRATA STORTI FOUNDATION )  102   498 - 498  2017.06

  Research paper, summary (international conference)  

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Awards 【 display / non-display 】

Awards 【 display / non-display 】

• 浜名湖シンポジウム研究助成演題

  2011.12  

• 日本肝臓学会 AASLD Travel Award

  2008.10  

• 浜名湖シンポジウム研究助成演題

  2006.12  

• 酸化ストレスと肝研究会 奨励賞

  2006.11  

• 第26回アルコール医学生物学研究会 優秀演題

  2006.03  

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Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• Development a novel immunotherapy for HCC targeted by BRG1

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2022.04

  -

  2025.03

   

  高田 弘一

  Authorship： Principal investigator

• MAGE-A4抗原を発現する切除不能進行・再発腫瘍に対するCAR-T細胞療法の医師主導第I相治験

  Project Year :

  2021.08

  -

  2024.03

   

  Authorship： Coinvestigator(s)

• Development a novel therapy for hepatocellular carcinoma by targeting STEAP1

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2019.04

  -

  2022.03

   

  Takada Kohichi

  　View Summary

  STEAP1 has emerged as an ideal target in cancer therapeutics. However, the functions of STEAP1 in hepatocellular carcinoma (HCC) remain unexplored. In the current study, we sought to characterize the biological roles of STEAP1 in HCC. STEAP1 transcripts are over-expressed and associated with poor clinical outcomes in patients with HCC in several publicly available datasets. STEAP1 silencing using small interfering RNA inhibited cell growth and was accompanied by G1 arrest induced by the suppression of cyclin D1 and the promotion of p27. STEAP1 silencing suppressed the expression of c-Myc, which we identified as a component in STEAP1 signal transduction by mining publicly available datasets, and confirmed this by PCR array. In conclusion, the knockdown of STEAP1 in HCC cells led to cell-growth inhibition involving G1 arrest by targeting the suppression of c-Myc. This study suggests a preclinical concept for STEAP1 as a druggable target in HCC.

• Development of a new treatment for colorectal cancer using the glucose metabolism characteristics.

  Grant-in-Aid for Scientific Research (B)

  Project Year :

  2017.04

  -

  2020.03

   

  Kato Junji

  　View Summary

  Metastatic / recurrent colorectal cancer is a disease with a poor prognosis, and the number of deaths continues to increase, and the development of more effective treatment methods is awaited. The FDG-PET examination, which utilizes the characteristics of increased sugar uptake in colorectal cancer, is useful for diagnosing colorectal cancer. Therefore, anticancer drugs using FDG as a carrier are promising as therapeutic agents for colorectal cancer. Therefore, we aimed to prepare an FDG-binding anticancer drug and examine its effect. A fluorescent reagent directly bound to FDG was prepared and examined, but no difference of anticancer effect from other sugar was observed. Considering that the stability of the reagent was a problem, we prepared a fluorescent reagent in which FDG was bound to liposomes, and found that it was taken up by cancer cells. In the future, we would like to promote the development of new anticancer agents that utilize this mechanism using FDG-binding liposomes.

• Reactive oxygen species play roles in multiple myeloma pathogenesis

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2016.04

  -

  2019.03

   

  Kohichi Takada

  　View Summary

  Six-transmembrane epithelial antigen of the prostate 1 (STEAP1), identified in prostate cancer cells as a cell surface protein, is over-expressed in a subset of human cancers. In cases of Ewing sarcoma, STEAP1 augmented cell proliferation and invasion and was accompanied by increased reactive oxygen spices (ROS) levels. Here, we characterized the biological impact of STEAP1 and ROS in multiple myeloma (MM) pathogenesis. STEAP1 expression negatively correlated with OS as determined from a publicly accessible gene expression profile data set. A loss-of-function approach in cultured MM cell lines revealed that STEAP1 silencing suppressed migration, invasion and bone marrow homing through inhibition of ROS production. Mechanistically, the inhibition of STEAP1 was associated with increased expression of anti-oxidant molecules regulated by the transcription factor, nuclear erythroid 2-related factor (NRF2), in MM cells. This study identified STEAP1 as a therapeutic target for MM.

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