Bibliographic Details
| Title: |
The molecular receptor NKBB enhances the persistence and anti-hepatocellular carcinoma activity of GPC3 CAR-T cells |
| Authors: |
Minghao Sui, Tiantian Liu, Xuanli Song, Ji Li, Han Ding, Yuqian Liu, Xinyu Wang, Huimin Liu, Yuchan Xue, Jianni Qi, Miao Zhang, Songbo Zhao, Qiang Zhu |
| Source: |
Pharmacological Research, Vol 212, Iss , Pp 107619- (2025) |
| Publisher Information: |
Elsevier, 2025. |
| Publication Year: |
2025 |
| Collection: |
LCC:Therapeutics. Pharmacology |
| Subject Terms: |
CAR-T, Hepatocellular carcinoma, GPC3, NKG2D, CTSL, IL-17, Therapeutics. Pharmacology, RM1-950 |
| More Details: |
Chimeric antigen receptor (CAR) T cells have encouraging results in the treatment of hematological malignancies. However, CAR-T therapy still faces numerous challenges against solid tumors, such as hepatocellular carcinoma (HCC), owing to heterogeneous antigen expression in tumor cells, limited persistence of CAR-T cells, etc. Therefore, to treat HCC more effectively, we connected the molecular receptor NKBB to a second-generation glypican-3 (GPC3) CAR to construct GC3328z-NKBB CAR-T cells, which have double specific targets of GPC3 and NKG2DLs (natural killer group 2, member D ligands), dual co-stimulation of CD28 and 41BB, and a single CD3ΞΆ chain. Our study showed that the molecular receptor NKBB conferred GPC3 CAR-T cells with enhanced migration and infiltration abilities towards HCC, higher central memory T (TCM) cell proportion and proliferation capacity, and reduced exhaustion level. GC3328z-NKBB CAR-T cells exhibited improved cytotoxicity against HCC cells and prolonged persistence. The cathepsin L/interleukin-17 (CTSL/IL-17) axis contributed to the superior anti-HCC activity of GC3328z-NKBB CAR-T cells. Overall, the molecular receptor NKBB significantly increased the persistence of GPC3 CAR-T cells, and GC3328z-NKBB CAR-T cells possessed potent anti-HCC activity in mice, providing a new strategy for the potential improvement of adoptive T cell therapy in the treatment of HCC. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1096-1186 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S1043661825000441; https://doaj.org/toc/1096-1186 |
| DOI: |
10.1016/j.phrs.2025.107619 |
| Access URL: |
https://doaj.org/article/b1b929dc43cc4de28d67375823281ca2 |
| Accession Number: |
edsdoj.b1b929dc43cc4de28d67375823281ca2 |
| Database: |
Directory of Open Access Journals |
