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Long-term in vitro expansion ensures increased yield of central memory T cells as perspective for manufacturing challenges

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. and Heimann, A. and Obermayer, B. and Ciraolo, E. and Althoff, S. and Ruß, J. and Grunert, C. and Busse, A. and Bullinger, L. and Pezzutto, A. and Blankenstein, T. and 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
Date:18 February 2021
Official Publication:https://doi.org/10.1002/ijc.33523
PubMed:View item in PubMed

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