纳米酶在增强 GPC3-CAR-T 细胞浸润与肿瘤免疫治疗中的双向作用

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.

Lenv@BSA-PtNPs were designed using albumin as a solubilizer, embedding lenvatinib via hydrophobic interactions and facilitating in situ PtNPs generation. The nanoenzyme functions as a catalase, converting H 2 O 2 to O 2 , 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.

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.

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.