2B4 co-stimulation and dasatinib modulation enhance anti-CD19 CAR-NK-92 cell cytotoxicity.

ABSTRACT:

Introduction

Chimeric Antigen Receptor (CAR)-based therapies have transformed cancer treatment, especially in hematological malignancies. While the impact of co-stimulatory domains on CAR-T cell efficacy is well established, the optimal signaling modules for CAR-natural killer (CAR-NK) cells remain less defined. Identifying NK-tailored co-stimulatory domains is essential for maximizing CAR-NK cytotoxicity and clinical potential.

Methods

Using the NK-92 cell line as a controlled proof-of-concept platform, we engineered CAR19 constructs incorporating NK-specific co-stimulatory domains, including 2B4 and DAP12. We performed functional assays to quantify cytotoxicity and cytokine production, and conducted transcriptomic profiling to evaluate transcriptional programs associated w

SUBMITTER: Dos Santos MH 

PROVIDER: S-EPMC12741080 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature