title: A novel, polymer-coated oncolytic measles virus overcomes immune suppression and induces robust antitumor activity.
abstract: Although various therapies are available to treat cancers, including surgery, chemotherapy, and radiotherapy, cancer has been the leading cause of death in Japan for the last 30 years, and new therapeutic modalities are urgently needed. As a new modality, there has recently been great interest in oncolytic virotherapy, with measles virus being a candidate virus expected to show strong antitumor effects. The efficacy of virotherapy, however, was strongly limited by the host immune response in previous clinical trials. To enhance and prolong the antitumor activity of virotherapy, we combined the use of two newly developed tools: the genetically engineered measles virus (MV-NPL) and the multilayer virus-coating method of layer-by-layer deposition of ionic polymers. We compared the oncolytic effects of this polymer-coated MV-NPL with the naked MV-NPL, bothin vitroandin vivo. In the presence of anti-MV neutralizing antibodies, the polymer-coated virus showed more enhanced oncolytic activity than did the naked MV-NPLin vitro. We also examined antitumor activities in virus-treated mice. Complement-dependent cytotoxicity and antitumor activities were higher in mice treated with polymer-coated MV-NPL than in mice treated with the naked virus. This novel, polymer-coated MV-NPL is promising for clinical cancer therapy in the future.
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan; Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; Research Institute for Diseases of the Chest, Kyushu University, Fukuoka, Japan.
authors.forename: Kaname
authors.initials: K
authors.lastname: Nosaki
authors.affiliation: Department of Obstetrics and Gynecology, Ehime University , Toon, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hamada
authors.affiliation: Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University , Fukuoka, Japan.
authors.forename: Yuto
authors.initials: Y
authors.lastname: Takashima
authors.affiliation: Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University , Fukuoka, Japan.
authors.forename: Miyako
authors.initials: M
authors.lastname: Sagara
authors.affiliation: Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University , Fukuoka, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Matsumura
authors.affiliation: Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; Project Division of ALA Advanced Medical Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Miyamoto
authors.affiliation: Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University , Fukuoka, Japan.
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Hijikata
authors.affiliation: Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University , Fukuoka, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Okazaki
authors.affiliation: Research Institute for Diseases of the Chest, Kyushu University , Fukuoka, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
authors.affiliation: Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; Project Division of ALA Advanced Medical Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Kenzaburo
authors.initials: K
authors.lastname: Tani