633 Reconstruction of Vascularized Subcutaneous Liver Tissue for Minimally Invasive Cell Therapy Molecular Therapy Volume 23, Supplement 1, May 2015 Copyright © The American Society of Gene & Cell The[.]
Cancer – Targeted Gene and Cell Therapy II 631 Novel Polymer-Coated Stealth Oncolytic Measles Virus Overcame Immune Suppression and Induced Stronger Antitumor Activity Kaname Nosaki,1,2,4 Katsuyuki Hamada,3 Yuto Takishima,2 Miyako Sagara,2 Yumiko Matsumura,2 Shohei Miyamoto,2 Michiyo Okada,2 Yasuki Hijikata,2 Toshihiko Okazaki,2 Kazunari Yamada,2 Hiroyuki Inoue,2,4 Yoichi Nakanishi,4 Kenzaburo Tani.2 Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan; 2Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; 3Department of Obstetrics and Gynecology, Ehime University, Toon, Japan; 4Research Institute for Diseases of the Chest, Kyushu University, Fukuoka, Japan Background: Although there have recently been much progress in cancer treatment including surgery, chemotherapy and radiotherapy, cancers have long been the leading cause of death in Japan in the last 30 years and the development of new therapeutic modalities is imminently required As a new modality, there has recently been great interest in oncolytic virotherapy Particularly, measles virus is one of the candidate viruses expected for strong antitumor effects The efficacy of virotherapy, however, was strongly limited by the immune response of the host in previous clinical trials Methods: To enhance and prolong the antitumor activity of the virotherapy in vivo, we combined newly developed tools of the genetically engineered measles virus (MV-NPL) and multilayer virus coating method of layer-by-layer deposition of ionic polymers We compared the oncolytic effects of this polymer-coated MV-NPL with naked MV-NPL in vitro and in vivo Results: In the presence of anti-MV neutralizing antibodies, the polymer-coated virus showed more enhanced oncolytic activity than naked MV-NPL in vitro We also examined the antitumor immunity in virus treated mice Complement-dependent cytotoxicity activities in mice treated with polymer-coated MV-NPL were higher than those with naked virus and stronger antitumor activity was observed in these mice Conclusion: This novel polymer-coated MV-NPL may be promising for future clinical cancer therapy 632 Oncolytic Adenoviruses Targeted to the HPV E6 and E7 Oncoproteins as a Novel Treatment for Head & Neck Squamous Cell Carcinomas Christopher J LaRocca,1 Amanda Oliveira,1 Joohee Han,1 Julia Davydova,1 Ramon Alemany,2 Cristina Balagué,3 Mark Herzberg,4 Rajaram Gopalakrishnan,4 Masato Yamamoto.1 Department of Surgery, University of Minnesota, Minneapolis, MN; 2Institut Català d´Oncologia-IDIBELL, Barcelona, Spain; Almirall Prodesfarma, Barcelona, Spain; 4Department of Diagnostic & Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN Introduction: Recent reports have shown that the incidence of Human Papilloma Virus (HPV)-positive head and neck squamous cell carcinomas (HNSCC) has been steadily increasing HNSCCs are known to have a high recurrence rate and compared to their HPV-negative counterparts, these tumors have a unique biology which necessitates the development of novel treatment modalities The HPV E6 and E7 oncoproteins are attractive therapeutic targets as they interact with key cell cycle regulatory components, namely p53 and pRb Our research group has applied conditionally replicating oncolytic adenoviruses (CRAd) with modifications in the E1a region of the genome allowing for selective replication in E6 and E7 expressing HNSCCs Methods: The in vitro transduction efficiency of E1-deleted luciferase expressing vectors with fiber modifications was assessed in multiple Molecular Therapy Volume 23, Supplement 1, May 2015 Copyright © The American Society of Gene & Cell Therapy HPV-positive and negative cell lines The CRAds were designed with a distinct deletion in the E1a region of the adenoviral genome (D24 and CB016) intended to allow for selective replication in HPVpositive HNSCC cells Additionally, the CRAds have a luciferase transgene in the E3 region that is expressed in a replication dependent manner By using a luciferase assay, the degree of viral replication was analyzed in numerous HNSCC cell lines In vitro cell viability following viral infection was analyzed with crystal violet and MTS assays A HPV-positive cell line (UPCI SCC 090) was used to establish subcutaneous tumors in female nude mice They were subsequently treated with either one intratumoral viral injection or four injections (given every fourth day) Results: The 5/3 fiber modification significantly increased viral infectivity in all tested HNSCC cell lines The 5/3 CB016 vector replicated selectively in HPV-positive cell lines, while the 5/3 D24 virus replicated in all cell lines regardless of HPV status Both of the vectors demonstrated profound cytocidal effects in the crystal violet and MTS assays For the in vivo experiments, a single intratumoral injection of virus demonstrated an anti-tumor effect for only one week following injection Given this limited effect, an additional in vivo experiment was performed to analyze the efficacy of multiple intratumoral injections (3.5 x1011 vp/injection) This setup resulted in statistically significant tumor growth suppression at day 26 when compared to the saline control group (p