論文 - 詳細
| RRC ID | 84384 |
|---|---|
| 著者 | Hou J, Uejima T, Tanaka M, Son YL, Hanada K, Kukimoto-Niino M, Yamaguchi S, Hashimoto S, Yokoyama S, Takemori T, Saito T, Shirouzu M, Kondo T. |
| タイトル | EVA1-antibody drug conjugate is a new therapeutic strategy for eliminating glioblastoma-initiating cells. |
| ジャーナル | Neuro Oncol |
| Abstract |
BACKGROUND:The discovery of glioblastoma (GBM)-initiating cells (GICs) has impacted GBM research. These cells are not only tumorigenic but also exhibit resistance to radiotherapy and chemotherapy. Therefore, it is crucial to characterize GICs thoroughly and identify new therapeutic targets. In a previous study, we successfully identified epithelial-V-like antigen 1 (EVA1) as a novel functional factor specific to GICs. METHODS:Hybridoma cells were generated by immunizing BALB/c mice with EVA1-Fc fusion protein. The reactivity of the supernatant from these hybridoma cells was examined using EVA1-overexpressing cells and GICs. Candidate antibodies were further selected using Biacore surface plasmon resonance analysis and 2 cytotoxicity assays-antibody-dependent cell cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Among the antibodies, the cytotoxicity of the B2E5-antibody drug conjugate (B2E5-ADC) was evaluated by both adding it to cultured GICs and injecting it into GIC tumor-bearing brains. RESULTS:B2E5 demonstrated a high affinity for human EVA1 and effectively killed both EVA1-expressing cell lines and GICs in culture through ADCC and CDC. B2E5-ADC also exhibited strong cytotoxicity to GICs in culture and prevented their tumorigenesis in the brain when administered intracranially to the tumor-bearing brain. CONCLUSION:Our data indicate that B2E5-ADC is a new and promising therapeutic strategy for GBM. |
| 巻・号 | 27(3) |
| ページ | 682-694 |
| 公開日 | 2025-3-7 |
| DOI | 10.1093/neuonc/noae226 |
| PII | 7848664 |
| PMID | 39470407 |
| PMC | PMC11889714 |
| MeSH | Animals Antibody-Dependent Cell Cytotoxicity Brain Neoplasms* / drug therapy Brain Neoplasms* / immunology Brain Neoplasms* / metabolism Brain Neoplasms* / pathology Cell Line, Tumor Glioblastoma* / drug therapy Glioblastoma* / immunology Glioblastoma* / metabolism Glioblastoma* / pathology Humans Immunoconjugates* / pharmacology Immunoconjugates* / therapeutic use Mice Mice, Inbred BALB C Mice, Nude Neoplastic Stem Cells* / drug effects Neoplastic Stem Cells* / immunology Neoplastic Stem Cells* / pathology Tumor Cells, Cultured Xenograft Model Antitumor Assays |
| IF | 10.247 |
| リソース情報 | |
| ヒト・動物細胞 | DAUDI(RCB1640) |