Academic Journal
Phase I trial of inducible caspase 9 T cells in adult stem cell transplant demonstrates massive clonotypic proliferative potential and long-term persistence of transgenic T cells
| العنوان: | Phase I trial of inducible caspase 9 T cells in adult stem cell transplant demonstrates massive clonotypic proliferative potential and long-term persistence of transgenic T cells |
|---|---|
| المؤلفون: | Zhang, Ping, Raju, Jyothy, Ullah, Md Ashik, Au, Raymond, Varelias, Antiopi, Gartlan, Kate H, Olver, Stuart D., Samson, Luke D., Sturgeon, Elise, Zomerdijk, Nienke, Avery, Judy, Gargett, Tessa, Brown, Michael P., Coin, Lachlan J., Ganesamoorthy, Devika, Hutchins, Cheryl, Pratt, Gary R, Kennedy, Glen A., Morton, A. James, Curley, Cameron I., Hill, Geoffrey R., Tey, Siok-Keen |
| بيانات النشر: | American Association for Cancer Research |
| سنة النشر: | 2019 |
| المجموعة: | The University of Queensland: UQ eSpace |
| مصطلحات موضوعية: | Cancer Research, Oncology, 1306 Cancer Research, 2730 Oncology |
| الوصف: | Inducible caspase 9 () is a cellular safety switch that can make T-cell therapy safer. The purpose of this phase I trial was to investigate the use of -transduced T-cell addback in adult patients undergoing haploidentical stem cell transplantation for high-risk hematologic malignancies. Patients undergoing myeloablative, CD34-selected haploidentical stem cell transplantation were treated with 0.5-1.0 × 10/kg donor-derived -transduced T cells on day +25 or 26 post-transplant, with additional doses allowed for disease relapse, infection, or mixed chimerism. Three patients were enrolled. -transduced T cells were readily detectable by 4 weeks post-infusion in all patients and remained at high level (114 cells/μL, 11% of T cells) in 1 patient alive at 3.6 years. One patient developed donor-derived Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV-PTLD), which was followed by a marked expansion of T cells and cytokine release syndrome (CRS). These -transduced T cells infiltrated the affected lymph nodes and secreted IFNγ and IL-10. They peaked at 1,848 cells/μL and were found to be monoclonal by T-cell receptor (TCR) clonotype and oligoclonal by viral integrant analysis, representing a 6-log expansion of the dominant T-cell clone. These T cells were not autonomous and contracted with the resolution of EBV-PTLD, which did not recur.-transduced T cells could persist long-term. They retained very high clonotypic proliferative capacity and function, and could cause CRS in response to lymphoma development. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1078-0432 1557-3265 |
| Relation: | orcid:0000-0002-0343-1274; orcid:0000-0001-5008-6429; orcid:0000-0002-4300-455X; orcid:0000-0001-8149-6703; orcid:0000-0003-2994-0429; orcid:0000-0001-9567-382X; APP1053135; Not set; APP1054786 |
| الاتاحة: | https://espace.library.uq.edu.au/view/UQ:6fe6588 |
| رقم الانضمام: | edsbas.58C23D68 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 10780432 15573265 |
|---|