Akt inhibition enhances expansion of potent tumor-specific lymphocytes with memory cell characteristics.

ABSTRACT: Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) results in complete regression of advanced cancer in some patients, but the efficacy of this potentially curative therapy may be limited by poor persistence of TIL after adoptive transfer. Pharmacologic inhibition of the serine/threonine kinase Akt has recently been shown to promote immunologic memory in virus-specific murine models, but whether this approach enhances features of memory (e.g., long-term persistence) in TIL that are characteristically exhausted and senescent is not established. Here, we show that pharmacologic inhibition of Akt enables expansion of TIL with the transcriptional, metabolic, and functional properties characteristic of memory T cells. Consequently, Akt inhibition results in enhanc

SUBMITTER: Crompton JG 

PROVIDER: S-EPMC4384335 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature