Bidirectional roles of nanoenzymes in enhancing GPC3-CAR T cell infiltration and cancer immunotherapy
Year: 2025
Type: article
Abstract: BACKGROUND: Vascular abnormalities and hypoxia in solid tumors limit the efficacy of chimeric antigen receptor (CAR) T-cell therapy. This study proposes a biomimic nanoenzyme, Lenv@BSA-PtNPs, combining platinum nanoparticles (PtNPs) and lenvatinib, to address these challenges in a hepatocellular carcinoma (HCC) nonobese diabetic (NOD) mice model. METHODS: , downregulating hypoxia-inducible factor (HIF-1), and normalizing tumor vasculature. Its efficacy was evaluated in a glypican-3 (GPC3)-CAR T-cell therapy model for HCC. RESULTS: Lenv@BSA-PtNPs significantly improved tumor oxygenation, normalized vasculature, and enhanced GPC3-CAR T-cell infiltration into tumors. This led to potent antitumor effects and prolonged survival in the HCC mouse model. CONCLUSIONS: Lenv@BSA-PtNPs provide a simple and effective strategy to enhance CAR-T cell accumulation and efficacy by ameliorating hypoxia and normalizing tumor vasculature, offering a promising approach for improving CAR-T therapy in solid tumors.
Authors: Yu Xu, Jianping Liao, Jiahong Wang, Yuan Gao, Yuan Wu, Meiqin Gao, Wenwen Liu, Da Zhang, Wenmin Zhang, Aimin Huang
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,890
Awards: G3358597804, G3862150004
OpenAlex ID: W4411276761