title: An RNA Molecule Derived From Sendai Virus DI Particles Induces Antitumor Immunity and Cancer Cell-selective Apoptosis.
abstract: Inactivated Sendai virus (hemagglutinating virus of Japan; HVJ) envelope (HVJ-E) induces anticancer immunity and cancer cell-selective apoptosis through the recognition of viral RNA genome fragments by retinoic acid-inducible gene-I (RIG-I). Here, we discovered that the "copy-back" type of defective-interfering (DI) particles that exist in the Cantell strain of HVJ induced the human PC3 prostate cancer cell death more effectively than the Sendai/52 strain or Cantell strain, which contain fewer DI particles. DI particle genomic RNA (~550 bases) activated proapoptotic genes such as Noxa and/or TNF-related apoptosis-inducing ligand (TRAIL) in human prostate cancer cells to induce cancer cell-selective apoptosis. DI particle-derived RNA was synthesized by in vitro transcription (in vitro transcribed (IVT)-B2). IVT-B2 RNA, which has a double-stranded region in its secondary structure, promoted a stronger anticancer effect than IVT-HN RNA, which does not have a double-stranded region in its secondary structure. The intratumoral transfection of IVT-B2 significantly reduced the volume of a human prostate tumor and induced tumor cell apoptosis in the xenograft mouse model. Moreover, the involvement of natural killer (NK) cells in IVT-B2-RNA-induced anticancer effects was also suggested. These findings provide a novel nucleic acid medicine for the treatment of cancer.
authors.affiliation: Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Liu
authors.affiliation: Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nishikawa
authors.affiliation: Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kaneda
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D003673:Defective Viruses / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases; D050130:Oncolytic Virotherapy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000628:therapy*; D017346:Protein Serine-Threonine Kinases; D012330:RNA, Double-Stranded / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D012367:RNA, Viral / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D029082:Sendai virus / Q000235:genetics*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D012330:RNA, Double-Stranded; D012367:RNA, Viral; D053221:TNF-Related Apoptosis-Inducing Ligand; C408347:Nlk protein, mouse; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases