Evaluation of Newcastle disease virus mediated dendritic cell activation and cross-priming tumor-specific immune responses ex vivo.

Abstract

We have developed an oncolytic Newcastle disease virus (NDV) that has potent in vitro and in vivo anti-tumor activities and attenuated pathogenicity in chickens. In this ex vivo study using the same recombinant NDV backbone with GFP transgene (NDV-GFP, designated as rNDV), we found that rNDV induces maturation of monocyte-derived immature dendritic cells (iDCs) by both direct and indirect mechanisms, which promote development of antigen-specific T cell responses. Addition of rNDV directly to iDCs culture induced DC maturation, as demonstrated by the increased expression of costimulatory and antigen-presenting molecules as well as the production of type I interferons (IFNs). rNDV infection of the HER-2 positive human breast cancer cell line (SKBR3) resulted in apoptotic cell death, release of proinflammatory cytokines, and danger-associated molecular pattern molecules (DAMPs) including high-mobility group protein B1 (HMGB1) and heat shock protein 70 (HSP70). Addition of rNDV-infected SKBR3 cells to iDC culture resulted in greatly enhanced upregulation of the maturation markers and release of type I IFNs by DCs than rNDV-infected DCs only. When co-cultured with autologous T cells, DCs pre-treated with rNDV-infected SKBR3 cells cross-primed T cells in an antigen-specific manner. Altogether, our data strongly support the potential of oncolytic NDV as efficient therapeutic agent for cancer treatment.

• Authors: Qi Xu, Udaya S Rangaswamy, Weijia Wang, Scott H Robbins, James Harper, Hong Jin, Xing Cheng
• Journal: International journal of cancer (Int J Cancer) Vol. 146 Issue 2 Pg. 531-541 (01 15 2020) ISSN: 1097-0215 [Electronic] United States
• PMID: 31584185 (Publication Type: Journal Article)
• Copyright: © 2019 UICC.

Chemical References

• Interferon Type I
• RNA, Viral
• RNA, recombinant
• RNA

Topics

• Animals
• Chlorocebus aethiops
• Coculture Techniques
• Cross-Priming
• Dendritic Cells (immunology, metabolism)
• Female
• HeLa Cells
• Humans
• Immunotherapy (methods)
• Interferon Type I (immunology, metabolism)
• Neoplasms (immunology, therapy)
• Newcastle disease virus (genetics, immunology)
• Oncolytic Virotherapy (methods)
• Oncolytic Viruses (genetics, immunology)
• RNA (administration & dosage, genetics)
• RNA, Viral (administration & dosage, genetics)
• T-Lymphocytes (immunology)
• Vero Cells