Newcastle Disease Virus (NDV) co-expressing IL7 and IL15 modified tumor cells as a vaccine for cancer immunotherapy

Abstract

IL15 and IL7 are two cytokines essential for T cell development and homeostasis. In order to improve the antitumor activity by Newcastle Disease Virus (NDV)-modified tumor vaccine, we generated a recombinant NDV co-expressing IL15 and IL7 (LX/IL(15+7)) by incorporation of a 2A self-processing peptide into IL15 and IL7 using reverse genetics. B16 cells infected with LX/IL(15+7) expressed both IL15 and IL7 stably. The cytotoxicity assay showed that murine melanoma cells modified with LX/IL(15+7) could significantly enhance the antitumor immune response in vitro. Then, the antitumor effects of tumor vaccine modified with recombinant virus were tested in the murine tumor models. We observed strong antitumor responses induced by LX/IL(15+7)-modified tumor cells both in prophylaxis and therapeutic models. Although the tumor-infiltrating CD4⁺ T cells and CD8⁺ T cells were both increased, the antitumor activity of the tumor vaccine modified with LX/IL(15+7) was dependent on CD8⁺ T cells. Taken together, our data strongly indicated that tumor vaccine modified with NDV strain LX/IL(15+7) is a promising agent for cancer immunotherapy.

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