Funakoshi, Takeru

写真a

Affiliation

School of Medicine, Department of Dermatology (Shinanomachi)

Position

Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)

External Links

Profile 【 Display / hide

  • 電子顕微鏡による微細構造解析、皮膚病理学を研究テーマとしていた。その後、天疱瘡における自己抗体サブクラス解析を経て、皮膚がん領域の研究活動に従事するようになる。現在は、主に介入型の医師主導臨床試験の計画と実施を主たる研究テーマとし、日々の診療と並行して研究を遂行している。

Career 【 Display / hide

  • 2009.08
    -
    2010.07

    University of Pennsylvania, Department of Dermatology, Visiting Scholar

  • 2010.08
    -
    2014.09

    Keio University School of Medicine, Department of Dermatology, 助教

  • 2014.10
    -
    Present

    Keio University School of Medicine, Department of Dermatology, Assistant Professor

Academic Background 【 Display / hide

  • 1995.04
    -
    2001.03

    Keio University, School of Medicine

    Japan, University, Graduated

Academic Degrees 【 Display / hide

  • 博士(医学), Keio University, Dissertation

Matters concerning Career Achievements 【 Display / hide

  • 2015.06

    慶應義塾大学プレスリリース「創傷部にメラノーマ(ほくろのがん)が転移するしくみを解明 創傷が治癒する際に生じるペリオスチンが原因」

 

Research Areas 【 Display / hide

  • Dermatology

Research Keywords 【 Display / hide

  • Skin cancer

Research Themes 【 Display / hide

  • Clinical Trial on Skin Cancer, 

    2010.08
    -
    Present

 

Books 【 Display / hide

  • 皮膚科のくすりの使い方

    舩越建, じほう, 2019.08

    Scope: 悪性腫瘍(メラノーマ),  Contact page: 218-222

  • マイナー外科救急レジデントマニュアル

    Funakoshi Takeru, 医学書院, 2016.07

    Scope: 262-298

Papers 【 Display / hide

  • Adoptive cell therapy using tumor-infiltrating lymphocytes for melanoma refractory to immune-checkpoint inhibitors

    Hirai I., Funakoshi T., Kamijuku H., Fukuda K., Mori M., Sakurai M., Koda Y., Kato J., Mori T., Watanabe N., Noji S., Yaguchi T., Iwata T., Ohta S., Fujita T., Tanosaki R., Handa M., Okamoto S., Amagai M., Kawakami Y.

    Cancer Science (Cancer Science)   2021

    ISSN  13479032

     View Summary

    To evaluate the feasibility of adoptive cell therapy (ACT) using ex vivo-expanded tumor-infiltrating lymphocytes (TILs) in Japanese patients with melanoma who failed immune-checkpoint inhibitor therapy, an open-label, single-arm, pilot study was conducted. We investigated the immunological and genetic factors of the pretreatment tumor and expanded TILs that may be associated with the clinical response. The treatment protocol comprised preparation of TIL culture, lympho-depleting non-myeloablative preconditioning with cyclophosphamide and fludarabine, TIL infusion, and intravenous administration of low-dose IL-2. Three patients of clinical subtypes mucosal, superficial spreading, and acral melanoma underwent TIL-ACT. Most severe adverse events, including fever and leukopenia, were manageable with the supportive regimen specified in the protocol, suggesting that the TIL-ACT regimen is suitable for Japanese patients with melanoma. One patient showed a short-term partial response, one relatively long-stable disease, and one experienced disease progression. Whole-exome and transcriptional sequencing of isolated tumor cells and immunohistochemical analyses before TIL-ACT revealed various immunostimulatory factors, including a high tumor mutation burden and immune cell-recruiting chemokines, as well as various immunosuppressive factors including TGF-β, VEGF, Wnt/β-catenin, and MAPK signaling and epithelial-to-mesenchymal transition, which might influence the efficacy of TIL-ACT. Our results imply mechanisms for the antitumor effect of and resistance to TIL-ACT. Further studies of immune-resistant mechanisms of TIL-ACT are warranted. This study is registered with the UMIN Clinical Trial Registry (UMIN 000011431).

  • Anti-PD-1 antibody therapy for epithelial skin malignancies: An investigator-initiated, open-label, single-arm, multicenter, phase II clinical trial (NMSC-PD1 Study)

    Ishii M., Hirai I., Tanese K., Fusumae T., Nakamura Y., Fukuda K., Uchi H., Kabashima K., Otsuka A., Yokota K., Yamazaki N., Namikawa K., Fujimura T., Takenouchi T., Yamamoto Y., Nishiguchi M., Sato Y., Amagai M., Funakoshi T.

    Medicine (Medicine)  99 ( 44 )  2020.10

     View Summary

    INTRODUCTION: Malignant cutaneous epithelial tumors comprise various skin malignancies originating from the cutaneous epithelium, including cutaneous squamous cell carcinoma, basal cell carcinoma, and malignant cutaneous adnexal tumors. Treatment options are limited, as the rarity of these tumors, especially among Asians, renders well-controlled clinical trials extremely challenging to conduct. Thus, we designed a clinical trial to evaluate the efficacy and safety of the anti-programmed cell death-1 (PD-1) monoclonal antibody nivolumab in patients with metastatic cutaneous squamous cell carcinomas and other rare metastatic cutaneous epithelial tumors. METHODS AND ANALYSIS: This is an open-label, single-arm, multicenter, phase 2 clinical trial involving patients with metastatic malignant cutaneous epithelial tumors. Nivolumab (480 mg) will be administered intravenously every 4 weeks for a maximum of 26 doses. The primary outcome of the study will be the response rate based on response evaluation criteria in solid tumors, version 1.1. Assuming a null hypothesis of a response rate ≤5% and an alternative hypothesis of a 25% response rate, a minimum of 26 patients are required to achieve a 5% two-sided type I error and 80% power based on the exact binomial distribution. Finally, a target cohort size of 30 patients was determined as some patient dropout will be expected. DISCUSSION: This is the first phase 2 clinical trial evaluating the efficacy and safety of the PD-1 inhibitor nivolumab in Asian patients with metastatic malignant cutaneous epithelial tumors. The findings of the study will contribute to the development of novel treatment approaches for patients with rare cutaneous malignancies, which remains an unmet clinical need. TRIAL REGISTRATION: Registry number: jRCT 2031190048.

  • Acute onset olfactory/taste disorders are associated with a high viral burden in mild or asymptomatic SARS-CoV-2 infections

    Nakagawara K., Masaki K., Uwamino Y., Kabata H., Uchida S., Uno S., Asakura T., Funakoshi T., Kanzaki S., Ishii M., Hasegawa N., Fukunaga K.

    International Journal of Infectious Diseases (International Journal of Infectious Diseases)  99   19 - 22 2020.10

    ISSN  12019712

     View Summary

    This study investigated, using cycle threshold (Ct) qPCR values, the association between symptoms and viral clearance in 57 patients with asymptomatic/mild SARS-CoV-2 infection. Patients with olfactory/taste disorders (OTDs) exhibited lower qPCR Ct values and longer time to negative qPCR than those without OTDs, suggesting an association between OTDs and high viral burden.

  • Anti-PD1 checkpoint inhibitor therapy in acral melanoma: a multicenter study of 193 Japanese patients

    Nakamura Y., Namikawa K., Yoshino K., Yoshikawa S., Uchi H., Goto K., Fukushima S., Kiniwa Y., Takenouchi T., Uhara H., Kawai T., Hatta N., Funakoshi T., Teramoto Y., Otsuka A., Doi H., Ogata D., Matsushita S., Isei T., Hayashi T., Shibayama Y., Yamazaki N.

    Annals of Oncology (Annals of Oncology)  31 ( 9 ) 1198 - 1206 2020.09

    ISSN  09237534

     View Summary

    Background: Acral melanoma (AM) is an epidemiologically and molecularly distinct entity that is underrepresented in clinical trials on immunotherapy in melanoma. We aimed to analyze the efficacy of anti-programmed cell death 1 (anti-PD-1) antibodies in advanced AM. Patients and methods: We retrospectively evaluated unresectable stage III or stage IV AM patients treated with an anti-PD-1 antibody in any line at 21 Japanese institutions between 2014 and 2018. The clinicobiologic characteristics, objective response rate (ORR, RECIST), survival estimated using Kaplan–Meier analysis, and toxicity (Common Terminology Criteria for Adverse Events 4.0.) were analyzed to estimate the efficacy of the anti-PD-1 antibodies. Results: In total, 193 patients (nail apparatus, 70; palm and sole, 123) were included in the study. Anti-PD-1 antibody was used as first-line therapy in 143 patients (74.1%). Baseline lactate dehydrogenase (LDH) was within the normal concentration in 102 patients (52.8%). The ORR of all patients was 16.6% (complete response, 3.1%; partial response, 13.5%), and the median overall survival (OS) was 18.1 months. Normal LDH concentrations showed a significantly stronger association with better OS than abnormal concentrations (median OS 24.9 versus 10.7 months; P < 0.001). Although baseline characteristics were similar between the nail apparatus and the palm and sole groups, ORR was significantly lower in the nail apparatus group [6/70 patients (8.6%) versus 26/123 patients (21.1%); P = 0.026]. Moreover, the median OS in this group was significantly poorer (12.8 versus 22.3 months; P = 0.03). Conclusions: Anti-PD-1 antibodies have limited efficacy in AM patients. Notably, patients with nail apparatus melanoma had poorer response and survival, making nail apparatus melanoma a strong candidate for further research on the efficacy of novel combination therapies with immune checkpoint inhibitors.

  • Basement membrane zone IgE deposition is associated with bullous pemphigoid disease severity and treatment results

    Kamata A., Kurihara Y., Funakoshi T., Takahashi H., Kuroda K., Hachiya T., Amagai M., Yamagami J.

    British Journal of Dermatology (British Journal of Dermatology)  182 ( 5 ) 1221 - 1227 2020.05

    Joint Work, Accepted,  ISSN  00070963

     View Summary

    © 2019 British Association of Dermatologists Background: A subset of patients with bullous pemphigoid (BP) show deposition of IgE in the basement membrane zone (BMZ), yet the relationship between BMZ IgE and the clinical presentation of BP remains unclear. Objectives: To investigate the relationship between IgE deposition, IgE levels in serum, and disease severity in patients with BP. Methods: We investigated IgE autoantibodies in 53 patients with BP by direct immunofluorescence (DIF), indirect immunofluorescence and enzyme-linked immunosorbent assay. Results: Of 53 patients with BP, 23 (43%) had IgE deposition, 10 (19%) of whom were IgE+ and 13 (25%) IgE± according to DIF analyses. Erosion/blister (E/B) Bullous Pemphigoid Disease Area Index (BPDAI) scores were significantly higher in IgE+ patients than in IgE− patients (n = 15), while no significant differences were found for urticaria/erythema BPDAI scores. IgE+ and IgE± patients took longer to reduce their E/B BPDAI score by 75% after systemic corticosteroid treatment. BP180-IgE levels were significantly higher among IgE+ patients than IgE± or IgE− patients (n = 10). Total IgE levels in the serum and blood eosinophil counts did not differ between IgE+, IgE± and IgE− patients. A significant correlation was detected between BP180-IgG and BP180-IgE, but not between BPDAI scores and any of BP180-IgG, BP180-IgE or blood eosinophil count. Conclusions: IgE deposition in the BMZ is associated with higher E/B BPDAI scores and longer treatment periods. We conclude that IgE binding in the BMZ may contribute to BP pathogenesis by promoting blister formation. What's already known about this topic?. BP180-IgE autoantibodies have an important role in the pathogenesis of bullous pemphigoid (BP). A subset of patients with BP display deposition of IgE within the basement membrane zone (BMZ) of skin tissue. What does this study add?. Patients with in vivo IgE deposition in the BMZ displayed higher erosion/blister Bullous Pemphigoid Disease Area Index (BPDAI) scores, while urticaria/erythema BPDAI scores were not significantly different. Patients with in vivo IgE deposition in the BMZ took longer to reduce their erosion/blister BPDAI score by 75% after systemic corticosteroid treatment. BP180-specific IgE levels in serum were higher among patients with linear IgE deposition in the BMZ than in those with granular or no IgE deposition.

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Papers, etc., Registered in KOARA 【 Display / hide

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Reviews, Commentaries, etc. 【 Display / hide

  • Autoimmune and inflammatory diseases occur in cases of drug-induced hypersensitivity syndrome but not in suspected cases

    Shiiya C., Ouchi T., Funakoshi T., Amagai M., Takahashi H.

    Journal of Dermatology (Journal of Dermatology)  48 ( 1 ) e45 - e46 2021.01

    ISSN  03852407

  • An adult case of X-linked chronic granulomatous disease with skin ulcer on the nose and internal canthus

    Inoue-Masuda Y., Hirai I., Yanagisawa E., Kurihara Y., Funakoshi T., Yamagami J., Amagai M., Kubo A.

    Journal of the European Academy of Dermatology and Venereology (Journal of the European Academy of Dermatology and Venereology)  34 ( 8 ) e388 - e391 2020.08

    ISSN  09269959

  • 乳房外パジェット病の病勢評価における血清CEAとCYFRA21-1のコンビネーションアッセイの有用性

    中村 善雄, 種瀬 啓士, 平井 郁子, 河上 裕, 天谷 雅行, 舩越 建

    日本皮膚科学会雑誌 ((公社)日本皮膚科学会)  129 ( 5 ) 1162 - 1162 2019.05

    ISSN  0021-499X

  • 全身性エリテマトーデスへ高用量ステロイド投与中に血管炎を生じた1例 IgA血管炎との合併か?

    朝比奈 泰彦, 田中 諒, 新川 宏樹, 舩越 建, 山田 裕揮, 太田 裕一朗, 仁科 直, 竹内 勤, 谷川 瑛子

    日本皮膚科学会雑誌 ((公社)日本皮膚科学会)  129 ( 5 ) 1182 - 1182 2019.05

    ISSN  0021-499X

  • 天疱瘡の寛解後に水疱性類天疱瘡を発症した1例

    田原海, 古市祐樹, 新川宏樹, 齋藤昌孝, 久保亮治, 天谷雅行, 舩越建, 山上淳

    第883回日本皮膚科学会東京地方会(城西地区) ((公社)日本皮膚科学会)  129 ( 6 ) 1348 - 1348 2019.05

    ISSN  0021-499X

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Presentations 【 Display / hide

  • 造影CTで活動性出血の所見なく、血腫除去時に判明したdeep dissecting hemtomaの1例

    小川夕貴, 伏間江貴之, 舩越建, 加藤達也, 岡部圭介, 小林秀, 天谷雅行, 山上淳

    第889回日本皮膚科学会東京地方会(城西地区) (東京) , 2020.02

  • 薬疹 経過中に自己抗体が出現した薬剤性過敏症症候群および疑い例の検討

    椎谷千尋, 大内健嗣, 舩越建, 天谷雅行, 高橋勇人

    第49回日本皮膚免疫アレルギー学会総会学術大会 (横浜) , 2019.11

  • 激しい腹痛と肝機能障害を伴い重症化した内臓播種性水痘ウィルス感染症の1例

    野澤優, 朝倉涼平, 山上淳, 天谷雅行, 舩越建

    第886回日本皮膚科学会東京地方会(城西地区) (東京) , 2019.10

  • 免疫チェックポイント阻害薬治療中に発症したが、投与を継続した水疱性類天疱瘡の1例

    新谷悠花, 齋藤京, 長谷衣佐乃, 舩越建

    第886回日本皮膚科学会東京地方会(城西地区) (東京) , 2019.10

  • 陰圧閉鎖療法が分層植皮固定に有用であった外陰部乳房外Paget病(EMPD)の1例

    及川紗由香, 新川宏樹, 平井郁子, 中村善雄, 大内健嗣, 舩越建

    第886回日本皮膚科学会東京地方会(城西地区) (東京) , 2019.10

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • [再生医療実用化研究事業] 進行性の悪性黒色腫および子宮頸癌に対する腫瘍浸潤Tリンパ球輸注療法

    2018.04
    -
    2021.03

    国立研究開発法人日本医療研究開発機構, 再生医療実用化研究事業, Yutaka Kawakami, Co-investigator

  • [難治性疾患等実用化研究事業 難治性疾患実用化研究事業] ステロイド治療抵抗性の天疱瘡患者を対象としたリツキシマブの医師主導治験

    2017.04
    -
    2020.03

    国立研究開発法人日本医療研究開発機構, 日本医療研究開発機構研究費, Masayuki Amagai, Co-investigator

  • [臨床研究・治験推進研究事業] 進行期乳房外パジェット病に対するトラスツズマブ、ドセタキセル併用療法の第II相臨床試験

    2017.04
    -
    2020.03

    国立研究開発法人日本医療研究開発機構, 臨床研究・治験推進研究事業, Principal Investigator

  • [革新的がん医療実用化研究事業] 進行期悪性黒色腫(末端黒子型)に対する非骨髄破壊性前処置併用での腫瘍浸潤Tリンパ球輸注療法の安全性試験

    2015
    -
    2017

    AMED(国立研究開発法人日本医療研究開発機構), 河上 裕

  • [「健康長寿の世界標準を創出するシステム医学・医療拠点」研究助成] マルチスペクトルカメラを用いた皮膚病変のコンピュータ診断補助システムの開発

    2014.04
    -
    2015.03

    科学技術振興機構(JST) COIプログラム, 舩越建

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Works 【 Display / hide

  • 日経産業新聞「免疫細胞、体外培養し投与、慶大が臨床試験、メラノーマ対象。」

    舩越建

    2016.09

    Other

  • 日経産業新聞「メラノーマの転移 解明」

    福田桂太郎, 舩越建, 天谷雅行

    2015.06

    Other

  • 週刊エコノミスト「+健康アプリ:72皮膚がん」

    舩越建

    2014.02

    Other

 

Courses Taught 【 Display / hide

  • PATHOPHYSIOLOGY AND CLINICAL ASSESSMENT

    2021

  • PATHOPHYSIOLOGICAL ISSUES IN CHRONIC CARE

    2021

  • LECTURE SERIES, DERMATOLOGY

    2021

  • PATHOPHYSIOLOGY AND CLINICAL ASSESSMENT

    2020

  • PATHOPHYSIOLOGICAL ISSUES IN CHRONIC CARE

    2020

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Courses Previously Taught 【 Display / hide

  • 皮膚科学

    学校法人慶應義塾大学, 2018

  • Dermatology

    Keio University, 2017

  • 皮膚科学講義「真皮、皮下脂肪組織の疾患」「代謝異常症」2016/11/24

    Keio University, 2016

  • 皮膚科学講義「真皮、皮下脂肪組織の疾患」「代謝異常症」2015/11/19     

    Keio University, 2015

  • 皮膚科学講義「真皮、皮下脂肪組織の疾患」2013/11/25

    Keio University, 2013

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Memberships in Academic Societies 【 Display / hide

  • Japanese Dermatological Association, 

    2001
    -
    Present

Committee Experiences 【 Display / hide

  • 2017.04
    -
    Present

    乳房外パジェット病ガイドライン作成委員, 乳房外パジェット病ガイドライン作成委員会