GC3328z-NKBB CAR-T

GC3328z-NKBB CAR-T is an **advanced chimeric antigen receptor T-cell therapy** designed for the treatment of **hepatocellular carcinoma (HCC)**. This engineered T-cell therapy incorporates multiple innovative features to enhance its therapeutic efficacy against solid tumors. The construct targets **glypican-3 (GPC3)**, a tumor-associated antigen highly expressed in HCC, while simultaneously incorporating the **NKBB molecular receptor** that recognizes **NKG2D ligands (NKG2DLs)**. This dual-targeting approach provides the therapy with two specific antigen recognition domains. The CAR design includes **dual costimulatory signaling** through both **CD28 and 4-1BB (CD137)** endodomains, along with a single **CD3ζ signaling chain**. The NKBB molecular receptor component significantly enhances the therapy's performance by conferring improved **migration and infiltration abilities** into tumor tissue, increasing the proportion of **central memory T cells (TCM)**, enhancing **proliferation capacity**, and reducing T-cell **exhaustion**. Preclinical studies demonstrated that the **cathepsin L/interleukin-17 (CTSL/IL-17) axis** contributes to the superior anti-HCC activity of this therapy. In mouse models, GC3328z-NKBB CAR-T cells showed **prolonged persistence** and **enhanced cytotoxicity** against HCC cells compared to conventional GPC3 CAR-T cells without the NKBB component. This therapy represents a novel strategy for improving adoptive T-cell therapy effectiveness in treating solid tumors, particularly hepatocellular carcinoma.