Interleukin-21 engineering enhances CD19-specific CAR-NK cell activity against B-cell lymphoma via enriched metabolic pathways.

ABSTRACT:

Background

NK cells engineered to express interleukin-15 (IL-15) and a CD19-targeted chimeric antigen receptor (CAR) have been used to treat patients with relapsed and/or refractory B cell malignances, demonstrating encouraging outcomes and favorable safety profile. However, the effect of IL-21 in CAR-NK cell therapy remains unknown.

Methods

CD19-specific CAR with 4-1BB costimulatory domain and cytokine IL-21 or IL-15 was constructed and transduced into peripheral blood (PB)-derived NK cells to produce CD19-CAR-IL21 NK cells (CAR-21) or CD19-CAR-IL15 NK cells (CAR-15), respectively. The phenotypic profile, transcriptomic characteristics, functionality and anti-tumor activity of CAR-21 NK cells and CAR-15 NK cells were compared.

Results

Compared with CAR-NK cells co-ex

SUBMITTER: He B 

PROVIDER: S-EPMC11967061 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature