Induced pluripotent stem cell-derived dendritic cell vaccine therapy genetically modified on the ubiquitin-proteasome system.
Gene Ther
; 30(7-8): 552-559, 2023 08.
Article
em En
| MEDLINE
| ID: mdl-36959396
ABSTRACT
We previously reported that dendritic cells (DCs) transduced with the full-length tumor-associated antigen (TAA) gene induced TAA-specific cytotoxic T lymphocytes (CTLs) to elicit antitumor responses. To overcome the issue of quantity and quality of DCs required for DC vaccine therapy, we focused on induced pluripotent stem cells (iPSCs) as a new tool for obtaining DCs and reported efficacy of iPSCs-derived DCs (iPSDCs). However, in clinical application of iPSDC vaccine therapy, further enhancement of the antitumor effect is necessary. In this study, we targeted mesothelin (MSLN) as a potentially useful TAA, and focused on the ubiquitin-proteasome system to enhance antigen-presenting ability of iPSDCs. The CTLs induced by iPSDCs transduced with MSLN gene (iPSDCs-MSLN) from healthy donors showed cytotoxic activity against autologous lymphoblastoid cells (LCLs) expressing MSLN (LCLs-MSLN). The CTLs induced by iPSDCs transduced ubiquitin-MSLN fusion gene exhibited higher cytotoxic activity against LCLs-MSLN than the CTLs induced by iPSDCs-MSLN. The current study was designed that peripheral T-cell tolerance to MSLN could be overcome by the immunization of genetically modified iPSDCs simultaneously expressing ubiquitin and MSLN, leading to a strong cytotoxicity against tumors endogenously expressing MSLN. Therefore, this strategy may be promising for clinical application as an effective cancer vaccine therapy.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Pluripotentes Induzidas
Idioma:
En
Revista:
Gene Ther
Assunto da revista:
GENETICA MEDICA
/
TERAPEUTICA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Japão