AKT inhibition generates potent polyfunctional clinical grade AUTO1 CAR T-cells, enhancing function and survival.

ABSTRACT:

Background

AUTO1 is a fast off-rate CD19-targeting chimeric antigen receptor (CAR), which has been successfully tested in adult lymphoblastic leukemia. Tscm/Tcm-enriched CAR-T populations confer the best expansion and persistence, but Tscm/Tcm numbers are poor in heavily pretreated adult patients. To improve this, we evaluate the use of AKT inhibitor (VIII) with the aim of uncoupling T-cell expansion from differentiation, to enrich Tscm/Tcm subsets.

Methods

VIII was incorporated into the AUTO1 manufacturing process based on the semiautomated the CliniMACS Prodigy platform at both small and cGMP scale.

Results

AUTO1 manufactured with VIII showed Tscm/Tcm enrichment, improved expansion and cytotoxicity in vitro and superior antitumor activity in vivo. Further, VIII indu

SUBMITTER: Mehra V 

PROVIDER: S-EPMC10503365 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature