Reference - Detail
| RRC ID | 45376 |
|---|---|
| Author | Tsukahara T, Iwase N, Kawakami K, Iwasaki M, Yamamoto C, Ohmine K, Uchibori R, Teruya T, Ido H, Saga Y, Urabe M, Mizukami H, Kume A, Nakamura M, Brentjens R, Ozawa K. |
| Title | The Tol2 transposon system mediates the genetic engineering of T-cells with CD19-specific chimeric antigen receptors for B-cell malignancies. |
| Journal | Gene Ther |
| Abstract |
Engineered T-cell therapy using a CD19-specific chimeric antigen receptor (CD19-CAR) is a promising strategy for the treatment of advanced B-cell malignancies. Gene transfer of CARs to T-cells has widely relied on retroviral vectors, but transposon-based gene transfer has recently emerged as a suitable nonviral method to mediate stable transgene expression. The advantages of transposon vectors compared with viral vectors include their simplicity and cost-effectiveness. We used the Tol2 transposon system to stably transfer CD19-CAR into human T-cells. Normal human peripheral blood lymphocytes were co-nucleofected with the Tol2 transposon donor plasmid carrying CD19-CAR and the transposase expression plasmid and were selectively propagated on NIH3T3 cells expressing human CD19. Expanded CD3(+) T-cells with stable and high-level transgene expression (~95%) produced interferon-γ upon stimulation with CD19 and specifically lysed Raji cells, a CD19(+) human B-cell lymphoma cell line. Adoptive transfer of these T-cells suppressed tumor progression in Raji tumor-bearing Rag2(-/-)γc(-/-) immunodeficient mice compared with control mice. These results demonstrate that the Tol2 transposon system could be used to express CD19-CAR in genetically engineered T-cells for the treatment of refractory B-cell malignancies. |
| Volume | 22(2) |
| Pages | 209-15 |
| Published | 2015-2-1 |
| DOI | 10.1038/gt.2014.104 |
| PII | gt2014104 |
| PMID | 25427612 |
| PMC | PMC5548386 |
| MeSH | Animals Antigens, CD19 / immunology* Cell Line, Tumor Coculture Techniques DNA Transposable Elements* Genetic Engineering Genetic Therapy Humans Immunotherapy, Adoptive Lymphoma, B-Cell / therapy* Mice Mice, Inbred BALB C Mice, Knockout Molecular Sequence Data NIH 3T3 Cells Neoplasm Transplantation Receptors, Antigen, T-Cell / biosynthesis Receptors, Antigen, T-Cell / genetics* Recombinant Fusion Proteins / biosynthesis Recombinant Fusion Proteins / genetics T-Lymphocytes / immunology* |
| IF | 4.128 |
| Times Cited | 11 |
| WOS Category | MEDICINE, RESEARCH & EXPERIMENTAL BIOTECHNOLOGY & APPLIED MICROBIOLOGY GENETICS & HEREDITY BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Resource | |
| Human and Animal Cells | K562 |