A novel fully human LAG-3 monoclonal antibody LBL-007 combined with PD-1 antibody inhibits proliferation, migration and invasion of tumor cells via blocking NF-κB pathway.
- Author:
Huinan ZHOU
1
;
Jianfei LIU
2
;
Chenglin WU
2
;
Kewei QIN
3
,
4
;
Lijun ZHOU
4
,
5
Author Information
1. The Second College of Clinical Medicine, Southern Medical University, Guangzhou 510515, China.
2. Central Laboratory, The Sixth Medical Centre, Chinese PLA General Hospital, Department of Otolaryngology Head and Neck Surgery, The Sixth Medical Centre, Chinese PLA General Hospital, Beijing 100048, China.
3. Central Laboratory, The Sixth Medical Centre, Chinese PLA General Hospital, Department of Otolaryngology Head and Neck Surgery, The Sixth Medical Centre, Chinese PLA General Hospital, Beijing 100048, China. *Corresponding authors, E-mail: qwfyqkw@
4. com.
5. The Second College of Clinical Medicine, Southern Medical University, Guangzhou 510515, China. *Corresponding authors, E-mail: hzzhoulj@
- Publication Type:Journal Article
- MeSH:
Humans;
Cell Proliferation/drug effects*;
Cell Movement/drug effects*;
Signal Transduction/drug effects*;
NF-kappa B/metabolism*;
Neoplasm Invasiveness;
Antibodies, Monoclonal/pharmacology*;
Programmed Cell Death 1 Receptor/antagonists & inhibitors*;
Cell Line, Tumor;
Antigens, CD/immunology*;
Lymphocyte Activation Gene 3 Protein;
A549 Cells;
I-kappa B Kinase/metabolism*;
Jurkat Cells;
Matrix Metalloproteinase 9/metabolism*
- From:
Chinese Journal of Cellular and Molecular Immunology
2025;41(5):398-405
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of LBL-007, a novel fully human lymphocyte activation gene 3 (LAG-3) monoclonal antibody, in combination with programmed cell death protein 1 (PD-1) antibody, on the invasion, migration and proliferation of tumor cells, and to elucidate the underlying mechanisms. Methods Human lymphocyte cells Jurkat were co-cultured with A549 and MGC803 tumor cell lines and treated with the isotype control antibody human IgG, LBL-007, anti-PD-1 antibody BE0188, or tumor necrosis factor-alpha (TNF-α, the NF-κB signaling pathway agonist). Tumor cell proliferation was assessed using a colony formation assay; invasion was measured by TranswellTM assay; migration was evaluated using a wound healing assay. Western blotting was employed to determine the expression levels of NF-κB pathway-related proteins: IκB inhibitor kinase alpha (Ikkα), phosphorylated Ikkα (p-IKKα), NF-κB subunit p65, phosphorylated p65 (p-p65), NF-κB Inhibitor Alpha (IκBα), phosphorylated IκBα (p-IκBα), matrix metalloproteinase 9 (MMP9), and MMP2. Results Compared with the control and IgG isotype groups, LBL-007 and BE0188 significantly reduced tumor cell proliferation, invasion, and migration. They also decreased the phosphorylation of p-IKKα, p-p65 and p-IκBα, and the expression of MMP9 and MMP2 of tumor cells in the co-culture system. The combined treatment of LBL-007 and BE0188 enhanced inhibitory effects. Treatment with the NF-κB signaling pathway agonist TNF-α reversed the suppressive effects of LBL-007 and BE0188 on tumor cell proliferation, invasion, migration, and NF-κB signaling. Conclusion LBL-007 and anti-PD-1 antibody synergistically inhibit the invasion, migration, and proliferation of A549 and MGC803 tumor cells by blocking the NF-κB signaling pathway.
