Autologous Tumor Vaccine Modified with Recombinant New Castle Disease Virus Expressing IL-7 Promotes Antitumor Immune Response

摘要

Autologous tumor vaccine modified with nonlytic Newcastle disease virus (ATV-NDV) is a promising vaccine for cancer immunotherapy. IL-7 plays a critical role in lymphocyte development and homeostasis. To improve the efficacy of ATV-NDV, we inserted the murine IL-7 gene into the genome of nonlytic NDV strain LX using reverse genetic system. The insertion of the IL-7 gene neither affected the main features of NDV replication nor its tumor selectivity. The gene product was biologically active and stable. Then we tested the antitumor effects of the autologous tumor vaccine modified with LX/(IL-7) in the murine tumor models. We showed that tumor cells modified with LX/IL-7 induced a strong antitumor activity both in prophylaxis and therapeutic models. The IFN-γ production and the cytotoxicity of tumor-specific CD8+ T cells were significantly enhanced after immunization with tumor cells modified with LX/(IL-7) in both models. Although the tumor-infiltrating CD4+ T cells and CD8+ T cells were both increased and their IFN-γ productions also were upregulated, the antitumor activity of the tumor vaccine modified with LX/(IL-7) was dependent on CD8+ T cells. Our results demonstrated that the autologous tumor vaccine modified with NDV strain LX/(IL-7) could promote the antitumor immune responses mediated by CD8+ T cells and significantly improve the efficacy of the ATV-NDV.