Reference - Detail
| RRC ID | 45467 |
|---|---|
| Author | Fujiwara H, Ochi T, Ochi F, Miyazaki Y, Asai H, Narita M, Okamoto S, Mineno J, Kuzushima K, Shiku H, Yasukawa M. |
| Title | Antileukemia multifunctionality of CD4(+) T cells genetically engineered by HLA class I-restricted and WT1-specific T-cell receptor gene transfer. |
| Journal | Leukemia |
| Abstract |
To develop gene-modified T-cell-based antileukemia adoptive immunotherapy, concomitant administration of CD4(+) and CD8(+) T cells that have been gene modified using identical HLA class I-restricted leukemia antigen-specific T-cell receptor (TCR) gene transfer has not yet been fully investigated. Here, using CD4(+) and CD8(+) T cells that had been gene modified with a retroviral vector expressing HLA-A*24:02-restricted and Wilms' tumor 1 (WT1)-specific TCR-α/β genes and siRNAs for endogenous TCRs (WT1-siTCR/CD4(+) T cells and WT1-siTCR/CD8(+) T cells), we examined the utility of this strategy. WT1-siTCR/CD4(+) T cells sufficiently recognized leukemia cells in an HLA class I-restricted manner and provided target-specific Th1 help for WT1-siTCR/CD8(+) T cells. By using a xenografted mouse model, we found that WT1-siTCR/CD4(+) T cells migrated to leukemia sites and subsequently attracted WT1-siTCR/CD8(+) T cells via chemotaxis. Therapy-oriented experiments revealed effective enhancement of leukemia suppression mediated by concomitant administration of WT1-siTCR/CD4(+) T cells and WT1-siTCR/CD8(+) T cells. Importantly, this augmented efficacy in the presence of WT1-siTCR/CD4(+) T cells was correlated with longer survival and enhanced formation of memory T cells by WT1-siTCR/CD8(+) T cells. Collectively, our experimental findings strongly suggest that this strategy would be clinically advantageous for the treatment of human leukemia. |
| Volume | 29(12) |
| Pages | 2393-401 |
| Published | 2015-12-1 |
| DOI | 10.1038/leu.2015.155 |
| PII | leu2015155 |
| PMID | 26104661 |
| MeSH | Animals CD4-Positive T-Lymphocytes / immunology* Cell Movement Female Genes, T-Cell Receptor* Genetic Engineering Histocompatibility Antigens Class I / physiology* Humans Immunotherapy, Adoptive* Leukemia / immunology Leukemia / therapy* Lymphocyte Activation Mice T-Lymphocytes, Cytotoxic / immunology WT1 Proteins / immunology* |
| IF | 8.665 |
| Times Cited | 8 |
| WOS Category | HEMATOLOGY ONCOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 3.0 |
| Resource | |
| Human and Animal Cells | 293T(RCB2202) |