# Lentiviral Dendritic Cell Vaccine Targeting Claudin-18.2 Elicits Potent Antitumor Immunity Against Gastric Cancer

## TL;DR

A new vaccine using dendritic cells and a lentivirus targeting CLDN18.2 shows strong anti-cancer effects in gastric cancer models.

## Contribution

A novel lentiviral dendritic cell vaccine targeting CLDN18.2 is shown to elicit potent antitumor immunity in gastric cancer.

## Key findings

- Lv-CLDN18.2-transduced DCs activated CD8+ T cells that effectively lysed CLDN18.2-positive gastric cancer cells in vitro.
- Vaccination with Lv-CLDN18.2-DCs significantly suppressed tumor growth and increased CD8+ T cell infiltration in a mouse model.
- The vaccine induced strong antigen-specific CTL responses and reduced tumor cell proliferation in vivo.

## 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 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.