Ex vivo AKT-inhibition facilitates generation of polyfunctional stem cell memory-like CD8⁺ T cells for adoptive immunotherapy.

ABSTRACT: Adoptive T cell therapy has shown clinical potential for patients with cancer, though effective treatment is dependent on longevity and potency of the exploited tumor-reactive T cells. Previously, we showed that ex vivo inhibition of AKT using the research compound Akt-inhibitor VIII retained differentiation and improved functionality of minor histocompatibility antigen (MiHA)-specific CD8⁺ T cells. Here, we compared a panel of clinically applicable AKT-inhibitors with an allosteric or adenosine triphosphate-competitive mode of action. We analyzed phenotype, functionality, metabolism and transcriptome of AKT-inhibited CD8⁺ T cells using different T cell activation models. Most inhibitors facilitated T cell expansion while preserving an early memory phenotype, r

SUBMITTER: Mousset CM 

PROVIDER: S-EPMC6169586 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature