Targeted delivery of cell medicine by cell surface modification with low molecular weight antibody

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H03516
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 90110:Biomedical engineering-related
• Research Institution: Kyoto University
• Principal Investigator: Higuchi Yuriko 京都大学, 薬学研究科, 准教授 (40402797)
• Co-Investigator(Kenkyū-buntansha): 山下 富義 京都大学, 薬学研究科, 教授 (30243041)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: ドラッグデリバリー / 間葉系幹細胞 / 低分子抗体

Outline of Final Research Achievements

Mesenchymal stem cells have anti-inflammatory, immunomodulatory, and multipotent differentiation potential, but disappear from the body relatively quickly after intravenous administration. In cell therapy, in vivo kinetic control of the therapeutic cells, such as accumulation of the cells at the target site of therapy and enhancement of their interaction with the target cells, may lead to improved therapeutic efficacy. In this study, we established a method to modify small molecule antibodies by introducing non-natural amino acids to align their orientation on the cell membrane. Furthermore, the modification of anti-ICAM1 VHH allowed the selective accumulation of mesenchymal stem cells to the inflamed liver. The results of this study are expected not only to increase the tissue-selective anti-inflammatory effects of mesenchymal stem cells, but also to lead to tissue regenerative medicine in the future.

Free Research Field

薬剤学、ドラッグデリバリー、生体医工学

Academic Significance and Societal Importance of the Research Achievements

本研究では、VHH修飾により、特定の組織への間葉系幹細胞の集積に成功した。これにより、組織選択的な治療効果と他の臓器での副作用の軽減を得ると共に、治療に必要な間葉系幹細胞数を減らすことで提供された細胞の有効活用が可能になる。また、間葉系幹細胞は肝臓、神経、筋肉ほか様々な組織への分化能を有し、再生医療への利用が期待されているが、間葉系幹細胞を静脈内投与すると、体内からの消失が早く分化には至らない。本研究の成果により治療対象組織に間葉系幹細胞を生着させることができれば、分化を利用した組織再生医療に繋がり、難治性疾患治療や臓器移植に代わる治療に貢献しうると期待できる。