KEIO RESEARCHERS INFORMATION SYSTEM

Profile 【 Display / hide 】

Profile 【 Display / hide 】

• Yuki Kagoya received his MD at the University of Tokyo in 2007 and completed clinical training for Internal Medicine, Hematology & Medical Oncology, and Transplantation Medicine. Dr. Kagoya was then involved in basic research on leukemia initiating cells during his PhD training. After obtaining PhD, he joined Dr. Naoto Hirano’s laboratory at Princess Margaret Cancer Centre, Toronto to be dedicated to research on cancer immunology and immunotherapy (2014-2018). He served on Aichi Cancer Center Research Institute as the Principal Investigator for 3 years prior to his recruitment to Keio University.

Career 【 Display / hide 】

Career 【 Display / hide 】

• 2007.04

  -

  2009.03

  Kanto Rosai Hospital, 内科

• 2013.04

  -

  2013.09

  The University of Tokyo, Faculty of Medicine University Hospital Heamatology and Oncology, Research Fellow

• 2013.10

  -

  2014.05

  The University of Tokyo, Faculty of Medicine University Hospital Heamatology and Oncology, Assistant Professor

• 2014.06

  -

  2018.05

  Princess Margaret Cancer Centre, Tumor Immunotherapy Program, Research Fellow

• 2018.06

  -

  2019.09

  The University of Tokyo, Faculty of Medicine University Hospital, Assistant Professor

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Academic Background 【 Display / hide 】

Academic Background 【 Display / hide 】

• 2001.04

  -

  2007.03

  The University of Tokyo, Faculty of Medicine, 医学科

• 2009.04

  -

  2013.03

  The University of Tokyo, Graduate School of Medicine

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

• Ph.D., The University of Tokyo, Coursework, 2013.03

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Life Science / Immunology (cancer immunology; cancer immunotherapy; cell therapy; molecular cell biology, hematology and medical oncology)

Research Keywords 【 Display / hide 】

Research Keywords 【 Display / hide 】

• Cancer immunotherapy

• Cancer immunology

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• 特集 腫瘍免疫とミトコンドリア ミトコンドリアリプログラミングによるCAR-T細胞療法の最適化

  近藤 泰介, 籠谷 勇紀

  医学のあゆみ (医歯薬出版)  296 ( 11 ) 1008 - 1013 2026.03

  Last author, Corresponding author, Accepted,  ISSN  00392359

  • Access to Document (DOI)
  • CiNii Research

• Constitutive STAT3 signaling, in comparison to STAT5, enhances CAR T cell efficacy and lowers systemic toxicity.

  Haosong Zhang, Yusuke Ito, Hitomi Kasuya, Taeko Hayakawa, Yang Li, Satoshi Inoue, Tsunenori Ouchida, Yuki Kagoya

  Cancer immunology research  2026.02

  Last author, Corresponding author, Accepted

  　View Summary

  Providing cytokine signaling is a key strategy to boost the efficacy of chimeric antigen receptor (CAR) T cell therapy. However, the individual roles of key downstream mediators, STAT3 and STAT5, remain incompletely understood. In this study, we engineered CAR T cells to express constitutively active mutants of STAT3 (Y640F; caSTAT3) and STAT5 (N642H; caSTAT5) to investigate their individual functions. In vitro, caSTAT3 CAR T cells exhibited enhanced effector function and a robust memory phenotype, with broader transcriptional changes involving both effector and memory associated genes compared to caSTAT5 CAR T cells. However, caSTAT3 CAR T cells failed to expand due to activation of apoptosis-related gene programs. In contrast, caSTAT5 CAR T cells demonstrated sustained proliferation over time. Despite the limited in vitro expansion, caSTAT3 CAR T cells exhibited reduced transgene toxicity in vivo and exerted durable antitumor activity in both leukemia and solid tumor models without significant off-tumor toxicity. Titrated expression of caSTAT3 maintained enhanced effector function without inducing apoptosis. On the other hand, caSTAT5 CAR T cells efficiently accumulated in tumors but also infiltrated non-tumor tissues, causing lethal systemic toxicity. Coexpression of caSTAT3 and caSTAT5 markedly enhanced the long-term proliferative capacity of CAR T cells, even in the absence of antigen stimulation or cytokine supplementation. These findings elucidate the distinct impacts of STAT3 and STAT5 activation on CAR T cell behavior and suggest that selective activation of STAT3 at optimal levels may improve CAR T cell efficacy while minimizing off-tumor toxicities.

  • Access to Document (DOI)

• Improving efficacy and safety of CAR-T cell therapy by manipulating cytokine signaling

  Kataoka Mirei, Ito Yusuke, Kagoya Yuki

  Japanese Journal of Transplantation and Cellular Therapy (Japanese Society for Transplantation and Cellular Therapy)  15 ( 1 ) 7 - 14 2026

  Last author, Corresponding author, Accepted

  　View Summary

  <p> Chimeric antigen receptor (CAR)-engineered T cell therapy has shown significant efficacy against hematological malignancies; however, its long-term efficacy remains suboptimal. Furthermore, solid tumors are highly resistant to CAR-T cell therapy. Cytokine signaling is important for anti-tumor activity of T cells. Modulating cytokine signaling can improve the efficacy and safety of CAR-T cell therapy. We will review representative studies on manipulating CAR-T cell functions using cytokine signaling.</p>

  • Access to Document (DOI)
  • CiNii Research

• Novel cancer immunotherapy using cell-derived membrane vesicles loaded with multiple immunomodulatory factors

  ITO Yusuke, OHTA Seiichi, KAGOYA Yuki

  Rinsho Ketsueki (The Japanese Society of Hematology)  67 ( 1 ) 3 - 10 2026

  Last author, Corresponding author, Accepted,  ISSN  04851439

  　View Summary

  <p>T細胞に対する二重特異性抗体（BsAb）はCD3抗体を介して抗腫瘍活性をT細胞に賦与するが，長期的な治療効果は未だ不十分である。T細胞に最適な抗腫瘍効果を誘導するには複合的なシグナルが必要であり，我々はBsAb，共刺激分子，サイトカインなどの分子群を同時に表面に搭載したナノサイズの細胞膜由来膜小胞の作製技術を確立した。B細胞性造血器腫瘍に対し，CD19を標的としたBsAbに加え，共刺激分子（CD80，4-1BBL），T細胞の増殖・長期生存に関わるサイトカイン（IL-7，IL-15）を搭載した膜小胞は，T細胞に抗原特異的な抗腫瘍活性を効率よく誘導した。また抗PDL1抗体，CTLA4抗体，IL-12，IL-18など腫瘍微小環境に作用する分子を搭載し，腫瘍内マクロファージの改変や免疫抑制シグナルの解除を行えることを示した。この手法は従来の抗体医薬と比較して多面的な免疫制御シグナルを誘導できる。</p>

  • Access to Document (DOI)
  • CiNii Research

• Computational optimization of chimeric antigen receptor

  Taisuke Kondo, Chisato Umehara, Yuki Kagoya

  Molecular Therapy (Elsevier BV)  33 ( 10 ) 4680 - 4681 2025.10

  Last author, Corresponding author, Accepted,  ISSN  1525-0016

  • Access to Document (DOI)

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

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

• Depletion of autoreactive B cells through chimeric autoantigen receptor system

  Kagoya, Yuki

  福澤諭吉記念慶應義塾学事振興基金事業報告集 (福澤基金運営委員会)  2024

• Development of adoptive immunotherapy against autoimmune diseases

  Kagoya, Yuki

  学事振興資金研究成果実績報告書 (慶應義塾大学)  2023

Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• 特集 腫瘍免疫とミトコンドリア ミトコンドリアリプログラミングによるCAR-T細胞療法の最適化

  近藤 泰介, 籠谷 勇紀

  医学のあゆみ (医歯薬出版)  296 ( 11 ) 1008 - 1013 2026.03

  ISSN  0039-2359

  • Access to Document (DOI)
  • CiNii Research

• Novel cancer immunotherapy using cell-derived membrane vesicles loaded with multiple immunomodulatory factors

  ITO Yusuke, OHTA Seiichi, KAGOYA Yuki

  Rinsho Ketsueki (The Japanese Society of Hematology)  67 ( 1 ) 3 - 10 2026

  ISSN  0485-1439

  　View Summary

  T細胞に対する二重特異性抗体（BsAb）はCD3抗体を介して抗腫瘍活性をT細胞に賦与するが，長期的な治療効果は未だ不十分である。T細胞に最適な抗腫瘍効果を誘導するには複合的なシグナルが必要であり，我々はBsAb，共刺激分子，サイトカインなどの分子群を同時に表面に搭載したナノサイズの細胞膜由来膜小胞の作製技術を確立した。B細胞性造血器腫瘍に対し，CD19を標的としたBsAbに加え，共刺激分子（CD80，4-1BBL），T細胞の増殖・長期生存に関わるサイトカイン（IL-7，IL-15）を搭載した膜小胞は，T細胞に抗原特異的な抗腫瘍活性を効率よく誘導した。また抗PDL1抗体，CTLA4抗体，IL-12，IL-18など腫瘍微小環境に作用する分子を搭載し，腫瘍内マクロファージの改変や免疫抑制シグナルの解除を行えることを示した。この手法は従来の抗体医薬と比較して多面的な免疫制御シグナルを誘導できる。

  • Access to Document (DOI)
  • CiNii Research

• Improving efficacy and safety of CAR-T cell therapy by manipulating cytokine signaling

  Kataoka Mirei, Ito Yusuke, Kagoya Yuki

  Japanese Journal of Transplantation and Cellular Therapy (Japanese Society for Transplantation and Cellular Therapy)  15 ( 1 ) 7 - 14 2026

  　View Summary

  Chimeric antigen receptor (CAR)-engineered T cell therapy has shown significant efficacy against hematological malignancies; however, its long-term efficacy remains suboptimal. Furthermore, solid tumors are highly resistant to CAR-T cell therapy. Cytokine signaling is important for anti-tumor activity of T cells. Modulating cytokine signaling can improve the efficacy and safety of CAR-T cell therapy. We will review representative studies on manipulating CAR-T cell functions using cytokine signaling.

  • Access to Document (DOI)
  • CiNii Research

• CAR-T細胞療法の有効性と安全性を高める試み—Improving the efficacy and safety of CAR-T cell therapy

  伊藤 雄介, 籠谷 勇紀

  血液内科 = Hematology / 血液内科編集委員会 編 (東京 : 科学評論社)  91 ( 4 ) 404 - 409 2025.10

  ISSN  2185-582X

  • CiNii Research

• Current status and challenges of CAR-T cell therapy for hematologic malignancies

  Kagoya Yuki

  Japanese Journal of Transplantation and Cellular Therapy (Japanese Society for Transplantation and Cellular Therapy)  14 ( 3 ) 121 - 129 2025

  　View Summary

  Chimeric antigen receptor (CAR)-engineered T-cell therapy can induce a high remission rate for B-cell tumors and multiple myeloma. However, a significant number of patients experience a relapse after a transient response. To improve the efficacy of CAR-T cell therapy, genetic modification focused on epigenetic factors and cytokine signaling has been actively explored to confer long-lived potential and resistance to exhaustion of CAR-T cells. Studies are also underway to prevent or mitigate therapeutic toxicities, such as cytokine release syndrome, which inevitably increase in proportion to the therapeutic effect. In addition, the risk of developing T-cell malignancies after CAR T-cell therapy is better understood, and there is increasing interest in the long-term safety of the therapy. Here, I will review recent studies and future directions in CAR T-cell therapy with respect to the above perspectives.

  • Access to Document (DOI)
  • CiNii Research

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Presentations 【 Display / hide 】

Presentations 【 Display / hide 】

• Reprogramming antitumor T cells to achieve a long-lived memory phenotype

  Mirei Kataoka, Yusuke Ito, Yuki Kagoya

  The 54th Annual Meeting of the Japanese Society for Immunology, 

  2025.12

  , 

  Oral presentation (general)

• Improving CAR-T cell therapy based on the molecular understanding of resistance mechanisms

  Yuki Kagoya

  The 54th Annual Meeting of the Japanese Society for Immunology, 

  2025.12

  , 

  Symposium, workshop panel (nominated)

• 二重特異性抗体療法の基礎知識

  Yuki Kagoya

  エプキンリWEBセミナー, 

  2025.12

  , 

  Other

• Reinforcing CAR-T/NK cell function based on molecular profiles

  Yuki Kagoya

  シン・モダリティセミナー 細胞治療編, 

  2025.12

  , 

  Public lecture, seminar, tutorial, course, or other speech

• Understanding the molecular mechanisms of CAR-T Cell therapy failure

  Yuki Kagoya

  The 53rd International Symposium of Princess Takamatsu Cancer Research Fund, 

  2025.11

  , 

  Symposium, workshop panel (nominated)

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

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

• 膠芽腫を標的とした疲弊耐性CAR-T細胞療法の開発

  2025.09

  -

  2028.08

  国立研究開発法人日本医療研究開発機構（AMED）, 橋渡し研究プログラム（大学発医療系スタートアップ支援プログラム）・シーズS1, Principal investigator

• 長期生存能を付与した肺癌に対するユニバーサルCAR-T細胞の開発

  2025.05

  -

  2028.03

  国立研究開発法人日本医療研究開発機構（AMED）, スマートバイオ創薬等研究支援事業, Principal investigator

• Balancing memory and effector T cell function through epigenetic modification

  2024.06

  -

  2026.03

  日本学術振興会, 挑戦的研究(萌芽), 挑戦的研究（萌芽）, Principal investigator

• 複合的な免疫応答を誘導できる抗腫瘍エクソソー ムの開発

  2024.04

  -

  2026.03

  国立研究開発法人日本医療研究開発機構（AMED）, 橋渡し研究プログラム 慶應義塾拠点 シーズA, Principal investigator

• Development of CAR-NK cell therapy with durable response through genetic manipulation

  2023.04

  -

  2026.03

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Principal investigator

  　View Summary

  キメラ抗原受容体（CAR）導入NK細胞は、造血器腫瘍に対しては臨床試験で有望な結果が報告されているものの、標準的な製造プロトコール、基本的な安全性、治療効果についてのデータは十分ではない。従来の理解と異なり、NK細胞にもT細胞に類似したメモリー様状態が存在し、その背景にある遺伝子発現、エピゲノムプロファイルの変化が明らかとなってきた。そこで本研究ではNK細胞のメモリー形成に中心的に関わる転写ネットワーク、エピジェネティックプロファイルを特定の遺伝子改変により再現することで、長期生存能・持続的な治療効果を誘導できるCAR-NK細胞療法を開発することを目標とした。
  本年度は、CAR-NK細胞に長期生存能を付与する遺伝子改変方法の探索を進め、有望な遺伝子標的を同定することに注力した。健常人由来末梢血単核球、または臍帯血細胞よりCD56陽性NK細胞を単離した上で、解析に用いた。特にNK細胞が終末分化状態に至る過程で発現変化を来す遺伝子に着目して、それらの遺伝子の過剰発現、及びCRISPR/Cas9によるノックアウトを行った際の既往変化をin vitroで解析した。その結果、遺伝子Aのノックアウトにより、NK細胞の長期的増殖能が顕著に向上することを見出した。細胞傷害活性には大きな変化がなかった。遺伝子AノックアウトCAR-NK細胞は、マスサイトメトリー解析においても広範な細胞表面抗原の発現変化を示し、またRNAシークエンスにおいてもコントロールＮＫ細胞と比較して1500個程度の遺伝子で有意な発現変化が確認された。
  次年度以降は遺伝子ＡノックアウトCAR-NK細胞の持続的抗腫瘍効果をin vivoにおける実験系で評価する計画である。

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Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• ADVANCED MEDICAL RESEARCH

  2026

• ADVANCED MEDICAL RESEARCH

  2026

• IMMUNOLOGY

  2026

• BASIC ONCOLOGY

  2026

• ADVANCED MEDICAL RESEARCH: PRACTICE

  2026

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