title: 13-Cis retinoic acid can enhance the antitumor activity of non-replicating Sendai virus particle against neuroblastoma.
abstract: Hemagglutinating virus of Japan-envelope (HVJ-E) is a drug delivery vector based on inactivated Sendai virus. Recently, antitumor activities were found for HVJ-E itself and clinical trials of HVJ-E for some malignant tumors are now ongoing. We investigated the in vitro and in vivo antitumor effects of HVJ-E against neuroblastoma, which is one of the most common malignant solid tumors in childhood. The sensitivity of human neuroblastoma cell lines to HVJ-E correlated with the expression level of gangliosides, Sialylparagloboside (SPG) and GD1a, receptors for HVJ. Among the cell lines, SK-N-SH was the most sensitive to HVJ-E in vitro and total SPG and GD1a expression was the highest. Complete eradication of subcutaneous tumors derived from SK-N-SH cells was achieved by intratumoral injection of HVJ-E in SCID mice and no recurrence was observed for more than 300 days after HVJ-E inoculation. In contrast, NB1 cells expressed the lowest amount of GD1a and SPG and were resistant to HVJ-E in vitro. The expression of GD1a increased by 13-cis retinoic acid (13cRA), which is a therapeutic drug for high risk neuroblastoma, thus leading to an improved sensitivity to HVJ-E in vitro. Only growth inhibition of the subcutaneous tumors derived from NB1 cells was achieved by HVJ-E in the SCID mice, but the combination of 13cRA and HVJ-E could achieve partial eradication of the xenograft and also lead to an improved prognosis. In conclusion, HVJ-E is a promising therapeutic modality for neuroblastoma and 13cRA can be used as an adjuvant to HVJ-E.
authors.affiliation: Division of Gene Therapy Science, Osaka University, Osaka, Japan.
authors.forename: Motonari
authors.initials: M
authors.lastname: Nomura
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimbo
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuzawa
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kaneda
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant / Q000379:methods; D005260:Female; D005677:G(M1) Ganglioside / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism; D005732:Gangliosides / Q000235:genetics / Q000378:metabolism; D005822:Genetic Vectors / Q000494:pharmacology; D006801:Humans; D015474:Isotretinoin / Q000494:pharmacology*; D051379:Mice; D016513:Mice, SCID; D009447:Neuroblastoma / Q000188:drug therapy / Q000235:genetics / Q000628:therapy* / Q000821:virology*; D050130:Oncolytic Virotherapy / Q000379:methods*; D029082:Sendai virus / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D005732:Gangliosides; D014759:Viral Envelope Proteins; C064020:ganglioside GD1alpha; D005677:G(M1) Ganglioside; D015474:Isotretinoin