CELL INTELLIGENCE · 肿瘤细胞治疗研究

Background: Claudin-18. 2 (CLDN18. 2) has emerged as a promising therapeutic target for gastric cancer due to its frequent and specific expression in malignant lesions. Dendritic cell (DC)-based vaccines represent a potent strategy for inducing antitumor immunity; however, their efficacy against solid tumors, such as gastric cancer, remains challenging. Methods: We developed a lentiviral vector encoding human CLDN18. 2 (Lv-CLDN18. 2) to generate antigen-loaded DC vaccines. In vitro, human monocyte-derived DCs were transduced and co-cultured with autologous T cells to induce cytotoxic T lymphocytes (CTLs). CTL function was assessed by flow cytometry, cytokine ELISA, and cytotoxicity assays against CLDN18. 2-positive gastric cancer cells. In vivo, the therapeutic efficacy of the DC vaccine was evaluated in a syngeneic mouse model subcutaneously inoculated with MFC-CLDN18. 2 cells. Results: We successfully produced high-titer Lv-CLDN18.

2 and established stable CLDN18. 2-positive gastric cancer cell lines. Lv-CLDN18. 2-transduced DCs exhibited a mature phenotype with upregulated co-stimulatory (CD80/CD86) and antigen-presenting molecules (HLA-ABC/DR). These DCs potently stimulated CTLs, leading to a significantly higher proportion of activated CD8 + CD25 + T cells, enhanced secretion of IFN-γ and TNF-α, and potent, specific lysis of CLDN18. 2-positive target cells in vitro.

In mouse models, vaccination with Lv-CLDN18. 2-DCs significantly suppressed tumor growth, which was associated with robust CD8 + T cell infiltration, reduced tumor cell proliferation (Ki-67), and decreased CLDN18. 2-positive tumor cells in vivo. Conclusions: Our study demonstrates that a CLDN18. 2-targeting DC vaccine can effectively induce potent antigen-specific CTL responses and elicit significant antitumor immunity in a preclinical model.

These findings provide a strong rationale for the clinical development of CLDN18. 2-directed DC-based immunotherapy for gastric cancer.