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

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. What's new Adoptive T cell therapy (ATT) is a risky procedure involving the isolation, ex‐vivo expansion, and reinfusion of tumor‐specific T cells. T cell manufacturing in ATT represents a bottleneck that can limit access to therapy for those patients that experience lymphopenia or lymphocyte dysfunctions. Here, the authors evaluated if minimally manipulative prolongation of in vitro expansion (>3 weeks with IL‐7 and IL‐15 cytokines) could result in enhanced T cell yields with preserved T cell functionality. The results demonstrate the feasibility of extended T cell expansion as an alternative for patients with insufficient numbers of T cells after the standard manufacturing procedure.