Abstract

This study successfully developed a dendritic cell (DC) vaccine targeting CLDN18.2 using a lentiviral vector (Lv-CLDN18.2). The lentivirus efficiently delivered the CLDN18.2 gene into DCs, enabling stable antigen expression and promoting DC maturation. In vitro experiments demonstrated that the vaccine activated specific CD8 + T cells, which effectively lysed CLDN18.2-positive gastric cancer cells. In a syngeneic mouse model, vaccination significantly suppressed tumor growth and was associated with increased intratumoral infiltration of CD8 + T cells. These results indicate that the lentivirus-based CLDN18.2-DC vaccine represents a promising immunotherapeutic strategy for treating gastric cancer. 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 se