Enhanced homing and efficacy of HER2-CAR T cells via CXCR5/CCR6 co-expression for HER2-positive NSCLC.

ABSTRACT:

Background

Chimeric antigen receptor T-cell (CAR T) therapy development represents a promising therapeutic strategy for HER2-positive non-small cell lung cancer (NSCLC), a subtype accounting for 1-5% of NSCLC cases. However, the clinical efficacy of CAR T cells remains limited by poor tumor infiltration. Here, we identify NSCLC-specific overexpression of the CXCL13 and CCL20 chemokines within the tumor microenvironment (TME) and develop a dual chemokine receptor strategy to overcome this barrier.

Methods

Western blotting and qRT-PCR were used to quantify chemokine receptor expression (CXCR5, CCR6) in NSCLC. Cytotoxicity and antigen recognition sensitivity of CXCR5-CCR6-HER2-CAR T cells against target cells were assessed using in vitro co-culture assays. In vitro proliferatio

SUBMITTER: Hu X 

PROVIDER: S-EPMC12326854 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature