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 】

• Comprehensive microRNA profiling coupled with function-based feature selection reveals a biomarker panel for predicting CAR-T cell exhaustion

  Nakamura N., Seo H., Hamada R., Kaneko H., Kagoya Y., Ohta S.

  Biochemical and Biophysical Research Communications 836 2026.10

  Last author, Corresponding author, Accepted,  ISSN  0006291X

  　View Summary

  Chimeric antigen receptor (CAR)-T cell exhaustion limits durable therapeutic efficacy, particularly under persistent antigen stimulation. While transcriptomic and epigenomic analyses have advanced the understanding of CAR-T cell exhaustion, the contribution of microRNAs (miRNAs) remains poorly characterized. Here, we present the first comprehensive landscape of miRNA expression in exhausted CAR-T cells generated using an in vitro repeated antigen stimulation model. Bulk miRNA sequencing identified 39 differentially expressed miRNAs between exhausted and control CAR-T cells. Subsequent reverse transcription-quantitative polymerase reaction validation reduced the candidate list to 18 miRNAs, which retained enrichment in pathways associated with cellular proliferation. To select an optimal biomarker panel for predicting exhaustion, we further applied functional analysis–based feature selection to minimize pathway redundancy, resulting in a six-miRNA panel. Machine learning models using these miRNAs achieved superior predictive performance (area under the curve = 0.958) compared with larger panels. Our findings identify miRNAs as key molecular hallmarks of CAR-T cell exhaustion and establish a rational framework for biomarker panel selection, with potential applications in CAR-T cell quality control, therapeutic response prediction, and manufacturing optimization.

  • Access to Document (DOI)

• CAR T Cells Targeting an Intracellular Leukemia Antigen Promiscuously Presented by Diverse HLA-II Alleles

  Evey Y.F. Zheng, Chung-Hsi Wang, Toshiki Ochi, Yota Ohashi, Fumie Ihara, Saori Fukao, Yusuke Ito, Giselle M. Boukhaled, Ben X. Wang, Dong-Hoon Han, Xinyu Wei, Priyanka Yolmo, Brian D. Burt, Kayoko Saso, Yukiko Matsunaga, Dalam Ly, Yuki Kagoya, Marcus O. Butler, Mark D. Minden, Naoto Hirano

  Blood Cancer Discovery (American Association for Cancer Research (AACR))  7 ( 5 ) 813 - 828 2026.08

  Last author, Corresponding author, Accepted,  ISSN  2643-3230

  　View Summary

  Abstract
  
  Chimeric antigen receptor (CAR) technology has revolutionized B-cell malignancy treatment by enabling T cells to effectively recognize and target lineage-specific surface antigens. However, CAR T cells show limited efficacy against myeloid neoplasms and solid tumors due to challenges in identifying suitable surface targets. In this study, we present a CAR targeting the intracellular WT1 oncoprotein, cross-presented by surface HLA class II (HLA-II) alleles. WT1-CAR T cells, derived from an antibody raised solely against a WT1 peptide, recognized the WT1330–348 peptide promiscuously presented by 18 out of 20 tested HLA-II alleles, overcoming traditional HLA restrictions. WT1-CAR T cells specifically recognized leukemic cells in a WT1- and HLA-II–dependent manner and mediated an antitumor response in vitro and in vivo. This approach broadens CAR-targetable antigens beyond traditional HLA restrictions and offers a promising therapeutic option to a wide and genetically diverse patient population.
  
  Significance:
  
  Leveraging the promiscuous binding of HLA-II–peptide complexes, we developed a CAR T-cell approach targeting an intracellular oncoprotein WT1 presented across diverse HLA-II families. Our study establishes a framework for CAR therapies against intracellular antigens, extending potential CAR T-cell applications to new cancer types and patient populations.

  • Access to Document (DOI)

• Identification of a shared antigen linking CD4 ⁺ T and B cell pathology in Sjögren’s disease

  Masaru Takeshita, Jun Inamo, Seiki Wakui, Ryosuke Nagashima, Takahiro Nishino, Kazuyuki Tsunoda, Satoshi Usuda, Hajime Inokuchi, Kazuyoshi Ishigaki, Takashi Sasaki, Yuki Kagoya, Katsuya Suzuki, Yuko Kaneko

  Science Advances (American Association for the Advancement of Science (AAAS))  12 ( 23 )  2026.06

  Last author, Corresponding author, Accepted

  　View Summary

  Sjögren’s disease (SjD) is an autoimmune disorder characterized by lymphocytic infiltration of exocrine glands. Although B cells producing anti-Ro60 autoantibodies are frequently found in salivary gland lesions, the antigen specificity of CD4 ⁺ T cells has remained unclear. Given accumulating evidence for T cell involvement in local autoantibody production, we comprehensively investigated Ro60 reactivity among lesion-infiltrating CD4 ⁺ T cells. Over 200 T cell receptors (TCRs) enriched in salivary glands from Japanese and Caucasian patients with SjD were screened using a TCR reporter system, identifying 13 Ro60-reactive TCRs predominantly expressed in T peripheral helper/T follicular helper subset, along with human leukocyte antigen alleles linked to SjD susceptibility. Ro60 was efficiently phagocytosed by antigen-presenting cells in the presence of autoantibodies and presented to Ro60-specific T cells, triggering their activation. This suggests that Ro60-specific B and CD4 ⁺ T cells orchestrate a pathological loop in salivary glands. Our study provides the first molecular identification of a major CD4 ⁺ T cell antigen in systemic autoimmunity and highlights coordinated T-B cell responses against a shared autoantigen.

  • Access to Document (DOI)

• Distinct roles of STAT3 and STAT5 in CAR T cell therapy

  Yuki Kagoya

  Molecular Therapy Oncology (Elsevier BV)  34 ( 2 ) 201224 - 201224 2026.06

  Lead author, Last author, Corresponding author, Accepted,  ISSN  2950-3299

  • Access to Document (DOI)

• 特集 デザイナー細胞の実用化と未来 がん免疫治療用T細胞をデザインする

  籠谷 勇紀

  医学のあゆみ (医歯薬出版)  297 ( 4 ) 297 - 302 2026.04

  Last author, Corresponding author, Accepted,  ISSN  00392359

  • Access to Document (DOI)
  • CiNii Research

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

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

• Development of adoptive immunotherapy for refractory systemic lupus erythematosus

  Kagoya, Yuki

  学事振興資金研究成果実績報告書 (慶應義塾大学)  2024

• 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 】

• 二重特性抗体療法の基礎と将来展望

  籠谷 勇紀

  Lymphoma Seminar in 函館, 

  2026.08

  , 

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

• Diverse roles of cytokine signaling in CAR-T cell therapy

  Yuki Kagoya

  The 30th Annual Meeting of Japanese Association of Cancer Immunology, 

  2026.07

  , 

  Symposium, workshop panel (nominated)

• CAR-T細胞療法の現状と今後：基礎から臨床まで

  籠谷 勇紀

  日本血液学会関東甲信越地方会, 

  2026.07

  , 

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

• 難治性がんに対する免疫細胞療法の再設計

  籠谷 勇紀

  がん研セミナー, 

  2026.07

  , 

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

• Cytokines that help or hinder CAR-T cell therapy

  Yuki Kagoya

  The 66th Annual Meeting of the Japanese Society of Lymphoma Research, 

  2026.06

  , 

  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 】

• IMMUNOLOGY

  2026

• BASIC ONCOLOGY

  2026

• ADVANCED MEDICAL RESEARCH: PRACTICE

  2026

• INTRODUCTION TO MEDICINE

  2026

• PHYSIOLOGY OF HUMAN BODY

  2026

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