Abstract 5912: Sentinel lymph node targeted therapy by oncolytic sendai virus suppresses micrometastasis of head and neck squamous cell carcinoma in an orthotopic nude mouse model
Authors: Tanaka Yuya , Araki Koji , Tanaka Shingo , Miyagawa Yoshihiro , Suzuki Hiroshi , Kamide Daisuke , Tomifuji Masayuki , Uno Kosuke , Harada Eiko , Yamashita Taku , Ueda Yasuji , Inoue Makoto , Shiotani Akihiro 
Published: August 2018

Abstract
Background: Lymph node metastasis is one of the most important prognostic factors in head and neck squamous cell carcinoma (HNSCC). In clinical N0 cases, however, it is difficult to decide whether we should select elective neck dissection or watchful waiting even at present. We recently reported the successful oncolytic virotherapy against head and neck cancer using recombinant Sendai virus vector (rSeV). We herein focus on sentinel lymph node (SLN)-targeted therapy by oncolytic Sendai virus as a novel less invasive therapy. The objectives of this study are to investigate rSeV migration into SLN, and to elucidate anti-tumor effect on SLN micrometastasis of HNSCC in an orthotopic nude mouse model.
Experimental design: We established SLN micrometastasis of HNSCC in an orthotopic nude mouse model. We inoculated HSC-3-M3, human highly metastatic tongue squamous carcinoma cells, into the left edge of the tongue, and two weeks after tumor inoculation we intratumorally injected a type of rSeV-GFP that selectively shows urokinase type plasminogen activator (uPA)-specific cell killing activity via cell-cell fusion, which is named “BioKnife”. We investigated rSeV migration into SLN by using immunostaining, RT-PCR, and in vivo imaging system. We also examined anti-tumor effect and its mechanisms through serial section examination of SLN by using anti-SeV antibody and the ApopTag peroxidase in situ apoptosis detection kit.
Results: rSeV migration into SLN was clearly visible by fluorescent signals of rSeV in SLN using immunostaining and in vivo imaging system, and clarified by significant increases of relative mRNA expressions of GFP compared to control group in both tongue and SLN using RT-PCR (p &lt; 0.05 respectively). Serial section examination of SLN showed that BioKnife selectively infected cancer cells and exhibited significant anti-tumor effect against SLN micrometastases compared to control groups (p &lt; 0.05). We also detected apoptosis in SLN micrometastasis infected by BioKnife.
Conclusions: This study demonstrated that BioKnife can migrate into metastatic SLN after intratumoral injection into primary tumor, and effectively suppresses SLN micrometastases in an orthotopic nude mouse model, suggesting that SLN targeted therapy of oncolytic rSeV has a great potential to provide a novel and promising alternative to elective neck dissection for clinical N0 patients with HNSCC.
Citation Format: Yuya Tanaka, Koji Araki, Shingo Tanaka, Yoshihiro Miyagawa, Hiroshi Suzuki, Daisuke Kamide, Masayuki Tomifuji, Kosuke Uno, Eiko Harada, Taku Yamashita, Yasuji Ueda, Makoto Inoue, Akihiro Shiotani. Sentinel lymph node targeted therapy by oncolytic sendai virus suppresses micrometastasis of head and neck squamous cell carcinoma in an orthotopic nude mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5912.