title: Vaccinia virus GLV-1h153 in combination with 131I shows increased efficiency in treating triple-negative breast cancer.
abstract: We investigated the therapeutic efficacy of a replication-competent oncolytic vaccinia virus, GLV-1h153, carrying human sodium iodide symporter (hNIS), in combination with radioiodine in an orthotopic triple-negative breast cancer (TNBC) murine model. In vitro viral infection was confirmed by immunoblotting and radioiodine uptake assays. Orthotopic xenografts (MDA-MB-231 cells) received intratumoral injection of GLV-1h153 or PBS. One week after viral injection, xenografts were randomized into 4 treatment groups: GLV-1h153 alone, GLV-1h153 and (131)I (∼ 5 mCi), (131)I alone, or PBS, and followed for tumor growth. Kruskal-Wallis and Wilcoxon tests were performed for statistical analysis. Radiouptake assay showed a 178-fold increase of radioiodine uptake in hNIS-expressing infected cells compared with PBS control. Systemic (131)I-iodide in combination with GLV-1h153 resulted in a 6-fold increase in tumor regression (24 compared to 146 mm(3) for the virus-only treatment group; P<0.05; d 40). We demonstrated that a novel vaccinia virus, GLV-1h153, expresses hNIS, increases the expression of the symporter in TNBC cells, and serves both as a gene marker for noninvasive imaging of virus and as a vehicle for targeted radionuclide therapy with (131)I.
authors.affiliation: 1Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10065, USA. Fongy@mskcc.org.
authors.forename: Sepideh
authors.initials: S
authors.lastname: Gholami
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Chen
authors.forename: Emil
authors.initials: E
authors.lastname: Lou
authors.forename: Laurence J
authors.initials: LJ
authors.lastname: Belin
authors.forename: Sho
authors.initials: S
authors.lastname: Fujisawa
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Longo
authors.forename: Nanhai G
authors.initials: NG
authors.lastname: Chen
authors.forename: Mithat
authors.initials: M
authors.lastname: Gönen
authors.forename: Pat B
authors.initials: PB
authors.lastname: Zanzonico
authors.forename: Aladar A
authors.initials: AA
authors.lastname: Szalay
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D051379:Mice; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism / Q000532:radiotherapy* / Q000628:therapy*; D014616:Vaccinia virus / Q000235:genetics / Q000502:physiology*
chemical_list: D007457:Iodine Radioisotopes
keywords: radiation therapy; symporter