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Long‐term in vitro expansion ensures increased yield of central memory T cells as perspective for manufacturing challenges
Author(s) -
Herda Stefanie,
Heimann Andreas,
Obermayer Benedikt,
Ciraolo Elisa,
Althoff Stefanie,
Ruß Josefine,
Grunert Corinna,
Busse Antonia,
Bullinger Lars,
Pezzutto Antonio,
Blankenstein Thomas,
Beule Dieter,
Na IlKang
Publication year - 2021
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.33523
Subject(s) - cd8 , t cell , cell therapy , memory t cell , in vivo , in vitro , cytotoxic t cell , adoptive cell transfer , medicine , lymphoma , cell , cancer research , immunology , stem cell , biology , immune system , microbiology and biotechnology , biochemistry
Adoptive T cell therapy (ATT) has revolutionized the treatment of cancer patients. A sufficient number of functional T cells are 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 antitumor 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.