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| Item Type: | Article |
|---|---|
| Title: | Long-term in vitro expansion ensures increased yield of central memory T cells as perspective for manufacturing challenges |
| Creators Name: | Herda, S., Heimann, A., Obermayer, B., Ciraolo, E., Althoff, S., Ruß, J., Grunert, C., Busse, A., Bullinger, L., Pezzutto, A., Blankenstein, T., Beule, D. and Na, I.K. |
| Abstract: | Adoptive T cell therapy (ATT) has revolutionized the treatment of cancer patients. A sufficient number of functional T cells is indispensable for ATT efficacy; however, several ATT dropouts have been reported due to T cell expansion failure or lack of T cell persistence in vivo. With the aim of providing ATT also to those patients experiencing insufficient T cell manufacturing via standard protocol, we evaluated if minimally manipulative prolongation of in vitro expansion (long-term (LT) >3 weeks with IL-7 and IL-15 cytokines) could result in enhanced T cell yield with preserved T cell functionality. The extended expansion resulted in a 39-fold increase of murine CD8(+) T central memory cells (Tcm). LT expanded CD8(+) and CD4(+) Tcm cells retained a gene expression profile related to Tcm and T memory stem cells (Tscm). In vivo transfer of LT expanded Tcm revealed persistence and anti-tumor capacity. We confirmed our in vitro findings on human T cells, on healthy donors and diffuse large B cell lymphoma patients, undergoing salvage therapy. Our study demonstrates the feasibility of an extended T cell expansion as a practicable alternative for patients with insufficient numbers of T cells after the standard manufacturing process thereby increasing ATT accessibility. |
| Keywords: | Cytokines, Adoptive Immunotherapy, T Lymphocytes, Translational Medical Research, Animals, Mice |
| Source: | International Journal of Cancer |
| ISSN: | 0020-7136 |
| Publisher: | Wiley |
| Volume: | 148 |
| Number: | 12 |
| Page Range: | 3097-3110 |
| Date: | 15 June 2021 |
| Official Publication: | https://doi.org/10.1002/ijc.33523 |
| PubMed: | View item in PubMed |
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