分子病態治療研究センター 遺伝子治療研究部

内堀 亮介

ウチボリ リヨウスケ  (ryosuke Uchibori)

基本情報

所属
自治医科大学 医学部難治性疾患遺伝子細胞治療開発講座 講師
学位
博士(医学)(自治医科大学)

J-GLOBAL ID
201401092855808609
researchmap会員ID
B000237426

外部リンク

論文

 46
  • Yoshihide Sehara, Yuki Hashimotodani, Ryota Watano, Kenji Ohba, Ryosuke Uchibori, Kuniko Shimazaki, Kensuke Kawai, Hiroaki Mizukami
    Molecular neurobiology 2024年4月27日  
    It is established that neurogenesis of dentate gyrus is increased after ischemic insult, although the regulatory mechanisms have not yet been elucidated. In this study, we focused on Ezh2 which suppresses gene expression through catalyzing trimethylation of lysine 27 of histone 3. Male gerbils were injected with adeno-associated virus (AAV) carrying shRNA targeting to Ezh2 into right dentate gyrus 2 weeks prior to forebrain ischemia. One week after ischemia, animals were injected with thymidine analogue to label proliferating cells. Three weeks after ischemia, animals were killed for histological analysis. AAV-mediated knockdown of Ezh2 significantly decreased the ischemia-induced increment of proliferating cells, and the proliferated cells after ischemia showed significantly longer migration from subgranular zone (SGZ), compared to the control group. Furthermore, the number of neural stem cells in SGZ significantly decreased after ischemia with Ezh2 knockdown group. Of note, Ezh2 knockdown did not affect the number of proliferating cells or the migration from SGZ in the non-ischemic condition. Our data showed that, specifically after ischemia, Ezh2 knockdown shifted the balance between self-renewal and differentiation toward differentiation in adult dentate gyrus.
  • Somsak Prasongtanakij, Sarinthip Preedagasamzin, Bunyada Jittorntrum, Usanarat Anurathapan, Teeraya Puavilai, Pimjai Niparuck, Pichika Chantrathammachart, Thanakrit Piyajaroenkij, Kitipong Uaesoontrachoon, Ryosuke Uchibori, Keiya Ozawa, Ken Ohmine, Suradej Hongeng
    European Journal of Haematology 2023年5月24日  査読有り
    Abstract Objectives Multiple myeloma (MM) accounts for 10% of hematologic malignancies. However, most of the patients suffered from relapsed/refractory disease. We would like to expand CAR T cell therapy to treat MM using our current platform. Methods BCMA CAR T lymphocytes were generated for volunteers or MM patients. The transduction efficiency was detected by the ddPCR technique. Immunophenotyping and exhaustion markers were monitored by flow cytometry. The efficacy of BCMA CAR T cells was tested using coculturing with BCMA CAR or mock, and the positive and negative targets, K562/hBCMA‐ECTM and K562, respectively. Results BCMA CAR T cells were generated from consented volunteers or MM patients and could be detected CAR BCMA expression at a mean of 4.07 ± 1.95 or 4.65 ± 1.21 copies/cell, respectively. Those modified T cells were primarily effector memory T cells. Our BCMA CAR T cells could explicitly eradicate the K562/hBCMA‐ECTM cell line while the K562 cell line survived. Interestingly, the BCMA CAR, mock T cells, and peripheral blood mononuclear cells from MM patients expressed similar levels of the exhaustion makers, TIM‐3, LAG‐3, and PD1. Conclusions Our BCMA CAR T cells, mainly effector/effector memory, could eliminate BCMA‐expressing cells in vitro and had similar levels of exhaustion markers among different populations.
  • 内堀 亮介, 大嶺 謙
    BIO Clinica 37(6) 525-529 2022年6月  
    医薬品の開発において、1970年代~80年代に次々と同定されたがん関連遺伝子を標的とするimatinibなどの低分子化合物が、薬剤としてがんに特異的に作用することが明確に示された。1980年代後半には、rituximabやtrastuzumabをはじめとする抗体医薬の開発が脚光を浴びてきた。近年、ヒト免疫メカニズムの理解の更なる深まりと遺伝子工学技術の発展により、患者自身のT細胞の働きを遺伝子操作で高めたCAR-T細胞を用いる治療法が、がんに対する革新的な細胞免疫療法として大きく期待されている。(著者抄録)
  • Ken Ohmine, Ryosuke Uchibori
    115(6) 799-810 2022年5月18日  査読有り
  • 内堀 亮介, 大嶺 謙
    血液内科 84(5) 730-736 2022年5月  

MISC

 30

書籍等出版物

 1

共同研究・競争的資金等の研究課題

 5