Antitumor effect and cellular immunity activation by murine interferon-beta gene transfer against intracerebral glioma in mouse

Cationic liposomes containing the human interferon-p (IFN-beta) gene induce marked growth inhibition in human glioma cells. In vivo experiments using an human glioma implanted into the brains of nude mice have demonstrated a definite growth-inhibitory effect, achieving complete tumor regression with multiple intratumoral injections of the gene. However, nude mouse studies are inadequate to evaluate antitumor effects fully, especially those relate d to activation of the host immune response. This article aimed to investig ate antitumor effects and immune response activation by murine IFN-beta gen e transfer in syngeneic mice. In vitro experiments demonstrated a stronger growth-inhibitory effect of liposomes containing the murine IFN-beta gene o n a GL261 mouse glioma cell line than exogenouslyadded murine IFN-beta. In in vivo experiments, intratumoral administration of liposomes containing th e murine IFN-beta gene resulted in a 16-fold reduction in the mean volume o f residual gliomas in the brains of C57BL/6 mice and massive infiltration o f cytotoxic T lymphocytes (CTL) within the residual tumor, while few CTL we re infiltrated in controls including murine IFN-beta, empty liposomes, nake d plasmid expressing murine IFN-beta, and liposomes containing beta-galacto sidase gene. In addition, 40% of mice treated with liposomes containing the murine IFN-beta gene were completely cured. These findings indicated that activation of cellular immunity participates in antitumor effects in vivo t ogether with direct effects of the IFN-beta gene.