PMID- 31584185 OWN - NLM STAT- MEDLINE DCOM- 20200219 LR - 20200219 IS - 1097-0215 (Electronic) IS - 0020-7136 (Linking) VI - 146 IP - 2 DP - 2020 Jan 15 TI - Evaluation of Newcastle disease virus mediated dendritic cell activation and cross-priming tumor-specific immune responses ex vivo. PG - 531-541 LID - 10.1002/ijc.32694 [doi] AB - 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. CI - (c) 2019 UICC. FAU - Xu, Qi AU - Xu Q AD - Microbial Sciences, AstraZeneca Ltd, South San Francisco, CA. FAU - Rangaswamy, Udaya S AU - Rangaswamy US AD - Microbial Sciences, AstraZeneca Ltd, South San Francisco, CA. FAU - Wang, Weijia AU - Wang W AD - Microbial Sciences, AstraZeneca Ltd, South San Francisco, CA. FAU - Robbins, Scott H AU - Robbins SH AD - Microbial Sciences, AstraZeneca Ltd, Gaithersburg, MD. FAU - Harper, James AU - Harper J AD - Oncology R&D, AstraZeneca Ltd, Cambridge, United Kingdom. FAU - Jin, Hong AU - Jin H AD - Microbial Sciences, AstraZeneca Ltd, South San Francisco, CA. FAU - Cheng, Xing AU - Cheng X AUID- ORCID: 0000-0002-7611-4763 AD - Microbial Sciences, AstraZeneca Ltd, South San Francisco, CA. LA - eng PT - Journal Article DEP - 20191101 PL - United States TA - Int J Cancer JT - International journal of cancer JID - 0042124 RN - 0 (Interferon Type I) RN - 0 (RNA, Viral) RN - 0 (RNA, recombinant) RN - 63231-63-0 (RNA) SB - IM MH - Animals MH - Chlorocebus aethiops MH - Coculture Techniques MH - *Cross-Priming MH - Dendritic Cells/*immunology/metabolism MH - Female MH - HeLa Cells MH - Humans MH - Immunotherapy/*methods MH - Interferon Type I/immunology/metabolism MH - Neoplasms/immunology/*therapy MH - Newcastle disease virus/genetics/immunology MH - Oncolytic Virotherapy/*methods MH - Oncolytic Viruses/genetics/immunology MH - RNA/administration & dosage/genetics MH - RNA, Viral/administration & dosage/genetics MH - T-Lymphocytes/immunology MH - Vero Cells OTO - NOTNLM OT - ex vivo OT - Oncolytic Newcastle disease virus OT - antitumor immune response OT - dendritic cells EDAT- 2019/10/05 06:00 MHDA- 2020/02/20 06:00 CRDT- 2019/10/05 06:00 PHST- 2019/04/19 00:00 [received] PHST- 2019/07/03 00:00 [revised] PHST- 2019/09/05 00:00 [accepted] PHST- 2019/10/05 06:00 [pubmed] PHST- 2020/02/20 06:00 [medline] PHST- 2019/10/05 06:00 [entrez] AID - 10.1002/ijc.32694 [doi] PST - ppublish SO - Int J Cancer. 2020 Jan 15;146(2):531-541. doi: 10.1002/ijc.32694. Epub 2019 Nov 1.