Signaling intact membrane-bound IL-15 enables potent anti-tumor activity and safety of CAR-NK cells.

ABSTRACT:

Background

Chimeric antigen receptor (CAR)-NK cells are a promising and safe alternative to CAR-T cells. However, the limited persistence in vivo restricts their clinical application and sustained therapeutic responses. IL-15 has been extensively used to improve CAR-NK cell persistence and effectiveness. Nevertheless, accumulation of IL-15 might induce uncontrolled proliferation of CAR-NK cells and thus lead to fatal side-effects. Therefore, it is essential to develop a safe and effective alternative strategy to improve the persistence and anti-tumor activity of CAR-NK cells.

Methods

A signaling intact membrane-bound IL-15 (mbIL-15) was designed by fusing IL-15 and full-length IL-15Rα and was systematically compared with secretory IL-15 (sIL-15) in a B7H3-targeting CA

SUBMITTER: Xu X 

PROVIDER: S-EPMC12518233 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature