Modulation of intracellular kinase signaling to improve TIL stemness and function for adoptive cell therapy.

ABSTRACT:

Introduction

Adoptive cellular therapy with tumor-infiltrating lymphocytes (TIL) has demonstrated promising clinical benefits in several solid tumors, but the efficacy of this therapy might be compromised by the "prone-to-exhaustion" phenotype of TIL and poor persistence in vivo. This calls for a robust expansion process to produce a large number of cells for clinical usage while at the same time maintaining favorable anti-tumor function and memory phenotype. Previous studies showed that the PI3K-AKT signaling pathway plays a key role in the regulation of T cell activation, differentiation and memory formation.

Method

We modulated the PI3K-AKT pathway in TIL isolated from cervical and ovarian cancer by application of AKT or PI3K inhibitors or CRISPR knockout of AKT1 and/or A

SUBMITTER: Feng H 

PROVIDER: S-EPMC9939193 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature