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

Autologous tumor vaccine modified with nonlytic Newcastle disease virus (ATV-NDV) is a promising vaccine for cancer immuno-therapy. 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-g 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-g 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. N ewcastle disease virus (NDV) has been considered to be a promising oncolytic agent that has been used clinically as an experimental therapy for .40 y (1–6). Many different hypotheses have been tested or are in the process of being developed regarding the use of NDV as a tumor treatment agent including 1) selective tumor cytolysis (7), 2) a nonspecific stim-ulator of the immune system by inducing cytokine productions (8), 3) a source of danger signals that can be recognized by different innate immune receptors including PKR (9) and RIG-I (10) in the cytoplasm and by TLRs in endosomes (11), and 4) as a viral vector for the transfer of immune regulatory genes with immu-notherapeutic potential (12). The clinical antitumor potential of NDV has been evaluated using oncolysates (13, 14), whole-cell vaccines containing non-lytic NDV (15, 16), or infection of patients with lytic NDV (17, 18). It has been shown that whole-cell vaccines can stimulate the immune system more efficiently than oncolysates (19, 20), probably because of the importance of the tumor cell membrane integrity needed for CTL activation. A novel type of whole-cell autologous tumor vaccine …