| | |  | | | | Record from Web of Science® | | | | | | |
| Rapid generation of combined CMV-specific CD4(+) and CD8(+) T-cell lines for adoptive transfer into recipients of allogeneic stem cell transplants |
|
|
| Author(s): Rauser G, Einsele H, Sinzger C, Wernet D, Kuntz G, Assenmacher M, Campbell JDM, Topp MS |
| Source: BLOOD Volume: 103 Issue: 9 Pages: 3565-3572 Published: MAY 1 2004 |
| Times Cited: 66 References: 36 |
| Abstract: Adoptive transfer of cytomegalovirus (CMV)-specific T cells can restore long-lasting, virus-specific immunity and clear CMV viremia in recipients of allogeneic stem cell transplants if CD4+ and CD8+ CMV-specific T cells are detected in the recipient after transfer. Current protocols for generating virus-specific T cells use live virus, require leukapheresis of the donor, and are time consuming. To circumvent these limitations, a clinical-scale protocol was developed to generate CMV-specific T cells by using autologous cellular and serum components derived from a single 500-mL blood draw. CMV-specific T cells were stimulated simultaneously with CMV-specific major histocompatibility complex class 1 (MHC 1)-restricted peptides and CMV antigen. Activated T cells were isolated with the interferon-gamma (IFN-gamma) secretion assay and expanded for 10 days. In 8 randomly selected, CMV-seropositive donors, 1.34 x 10(8) combined CD4(+) and CD8(+) CMV-specific T cells, on average, were generated, as determined by antigen-triggered IFN-gamma production. CMV-infected fibroblasts were efficiently lysed by the generated T cells, and CMV-specific CD4(+) and CD8(+) T cells expanded if they were stimulated with natural processed antigen. On the other hand, CD4(+) and CD8(+) T cell-mediated alloreactivity of generated CMV-specific T-cell lines was reduced compared with that of the starting population. In conclusion, the culture system developed allowed the rapid generation of allodepleted, highly enriched, combined CD4(+) and CD8(+) CMV-specific T cells under conditions mimicking good manufacturing practice. (C) 2004 by The American Society of Hematology. |
| Document Type: Article |
| Language: English |
| Reprint Address: Topp, MS (reprint author), Univ Tubingen, Med Klin 2, Otfried Muller Str 10, D-72076 Tubingen, Germany |
Addresses:
1. Univ Tubingen, Med Klin 2, D-72076 Tubingen, Germany
2. Miltenyi Biotec, Bergisch Gladbach, Germany |
| Publisher: AMER SOC HEMATOLOGY, 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA |
| Subject Category: Hematology |
| IDS Number: 822UJ |
| ISSN: 0006-4971 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |