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.

Oncolytic Newcastle disease virus activation of the innate immune response and priming of antitumor adaptive responses in vitro

“…The observation that direct infection of DCs by MEDI5395, a possible by-product of therapy, enhanced their function as antigen-presenting cells suggests a further mechanism by which MEDI5395 may impact the priming of antitumor immune T-cell response. A similar DC-maturing effect has been observed using an NDV-GFP virus [32]. Concomitant to this, release of IFN-γ by activated T cells, as observed in vitro here, may upregulate PD-L1 expression within the TME.…”

Newcastle Disease Virus Inhibits the Proliferation of T Cells Induced by Dendritic Cells In Vitro and In Vivo

“…Functional maturation of DCs is characterized by decreased antigen capture and efficient antigen presentation ( 22 ). Previous studies in the context of NDV have shown that although the expression of surface markers and cytokines is efficiently enhanced ( 3 , 4 ), DCs may remain non-functional as a consequence of apoptosis ( 5 ). In this study, in vitro results indicated that infective NDV acted as a potent inducer of DC maturation, accompanied by increased expression of MHC-I, MHC-II, CD40, CD80, and CD86 on the cell surface ( Figures 1A–E ), as well as the production of pro-inflammatory cytokines ( Figures 1F–H ).…”

“…It has been reported that NDV suppresses the innate immune response through V protein-mediated MDA5, phospho-STAT1 and MAVS degradation ( 1 , 2 ). NDV is reported to have distinct influences on dendritic cells (DCs) during the early stage of NDV infection, including activation of the DCs and cross-priming of naïve T cells into tumor-specific T cells ( 3 , 4 ). However, another study indicated that infection with a velogenic NDV strain could stimulate an extrinsic apoptosis pathway in DCs, resulting in inhibition of CD4 + T cell proliferation ( 5 ).…”

Mesenchymal stem cell carriers enhance anti‑tumor efficacy of oncolytic virotherapy (Review)

“…Firstly, tumor-associated antigens (TAAs) and neoantigens (TANs), which are released by tumor cells, are captured by antigen-presenting cells and are ultimately activated by tumor specific T cells in order to respond to tumor antigens (26,27). Secondly, OVs can promote immunogenic cell death by cell necrosis, immunogenic apoptosis and autophagic cell death (27)(28)(29)(30), subsequently releasing danger-associated molecular patterns (DAMPs), including ATP and high-mobility group box 1 protein (28,31,32). In addition, virus-induced tumor cell death also leads to the release of pathogen-associated molecular patterns (PAMPs), such as nucleic acids, proteins and viral capsid components (33,34).…”