Tumor Cells Modified with Newcastle Disease Virus Expressing IL-24 as a Cancer Vaccine

Abstract

Interleukin-24 (IL-24) is a promising agent for cancer immunotherapy that induces apoptosis of tumor cells and enhances T cell activation and function. In order to improve the antitumor activity induced by Newcastle disease virus (NDV)-modified tumor vaccine, we generated a recombinant NDV expressing IL-24 using reverse genetics. Irradiated tumor cells infected with LX/IL-24 showed stable IL-24 expression. The cytotoxicity assay showed that LX/IL-24-infected murine melanoma cells significantly enhanced the antitumor immune response in vitro . Then, the antitumor effects of virus-infected tumor cells were examined in the murine tumor models. LX/IL-24-infected tumor cells exhibited strong antitumor effects both in prophylaxis and therapeutic models. LX/IL-24-infected tumor cells increased infiltration of CD4 + T cells and CD8 + T cells in tumor sites, and the antitumor activity of the tumor vaccine modified with LX/IL-24 was dependent on CD8 + T cells. Taken together, our data well illustrates that LX/IL-24-modified tumor cells are a promising agent for cancer immunotherapy.

Newcastle Disease Virus at the Forefront of Cancer Immunotherapy

“…In a separate study using NDV Hitchner B1 strains engineered to express either murine IL-2, IFN-γ, and GM-CSF in vivo, only NDV expressing IL-2 led to a significant increase in overall animal survival when compared to parental NDV [82]. Similar results were recently demonstrated with a lentogenic recombinant NDV strain expressing IL-24 [84]. Optimal immune mechanisms for intratumoral targeting with oncolytic virus are unknown.…”

Exploring the Prospects of Engineered Newcastle Disease Virus in Modern Vaccinology

“…Thus, although NDV is naturally oncolytic, reverse genetics technology can be used to improve its properties to overcome the potential limitations associated with the use of the wild type virus. Recently, recombinant NDV engineered to express IL-24 has been shown to demonstrate improved oncolytic efficacy in murine melanoma models [143]. A summary of the approaches used in enhancing the oncolytic potential of NDV using reverse genetics is shown in Table 2.…”

Viruses as tools in gene therapy, vaccine development, and cancer treatment

“…When tested in HT29 colon cancer cells, rNDV-IL12 induced apoptosis as well as an immune response [ 104 ]. Likewise, IL-24 incorporated into the rNDV induced apoptosis and T-cell-mediated immunity against murine melanoma [ 173 ]. In a novel approach, a combined therapeutic and preventive anti-cancer vaccine was designed to coexpress IL-7 and IL-15.…”