Therapeutic vaccine targeting Epstein-Barr virus latent protein, LMP1, suppresses LMP1-expressing tumor growth and metastasis in vivo

Background: In endemic area, nasopharyngeal carcinoma (NPC) tumor cells harbor EBV latent infection and expresses viral antigens such as EBNA1, LMP1 and LMP2. In this study, we established a NPC-mimicry animal model and assessed the therapeutic potential of LMP1 vaccine. Methods: Animal models were established by injection of LMP1-expressing TC-1 cells in C57BL6/J mice subcutaneously or through tail veins. pcDNA3.1 empty vector or LMP1/pcDNA3.1 vaccine was delivered by a helium-driven gene gun. Effectiveness of vaccine was evaluated by measuring the tumor size and numbers of metastatic lung nodules. Circulating cytokines were evaluated by ELISArray. Populations of activated cytotoxic T lymphocytes (CTLs) and LMP1-specific T lymphocytes were evaluated by flow cytometry with CD8/CD107a double staining and interferon-γ ELISPOT assay, respectively. Results: LMP1 vaccine significantly suppressed tumor growth (n=3) and metastasis (n=4) in vivo. When vaccinated before tumor challenge, all mice in vaccine group were tumor-free, whereas all mice in the control group developed tumors within 2 weeks after tumor challenge (n=10). Cytokine ELISArray revealed elevation of a panel of proinflammatory cytokines in mice receiving LMP1 vaccine. Flow cytometry and interferon-γ ELISPOT assay revealed that LMP1 vaccine induced larger populations of activated CTLs and LMP1-specific T lymphocytes. Conclusions: This pre-clinical study provides a promising result that LMP1 vaccine suppresses LMP1-expressing tumor growth and metastasis in vivo.