1. Tumor-targeting adenovirus OBP-401 inhibits primary and metastatic tumor growth of triple-negative breast cancer in orthotopic nude-mouse models
- Author
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Yano, Shuya, Takehara, Kiyoto, Kishimoto, Hiroyuki, Tazawa, Hiroshi, Urata, Yasuo, Kagawa, Shunsuke, Bouvet, Michael, Fujiwara, Toshiyoshi, and Hoffman, Robert M
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Breast Cancer ,2.1 Biological and endogenous factors ,Aetiology ,Adenoviridae ,Animals ,Cell Line ,Tumor ,Disease Models ,Animal ,Female ,Humans ,Mammary Glands ,Animal ,Mice ,Mice ,Nude ,Neoplasm Metastasis ,Oncolytic Virotherapy ,Organ Specificity ,Telomerase ,Triple Negative Breast Neoplasms ,Xenograft Model Antitumor Assays ,GFP ,green fluorescent protein ,RFP ,red fluorescent protein ,OBP-401 ,TNBC ,adenovirus ,high-metastatic ,nude mouse ,triple-negative breast cancer ,variants ,Oncology and carcinogenesis - Abstract
Our laboratory previously developed a highly-invasive, triple-negative breast cancer (TNBC) variant using serial orthotopic implantation of the human MDA-MB-231 cell line in nude mice. The isolated variant was highly-invasive in the mammary gland and lymphatic channels and metastasized to lymph nodes in 10 of 12 mice compared to 2 of 12 of the parental cell line. In the present study, the tumor-selective telomerase dependent OBP-401 adenovirus was injected intratumorally (i.t.) (1 × 108 PFU) when the high-metastatic MDA-MB-231 primary tumor expressing red fluorescent protein (MDA-MB-231-RFP) reached approximately 500 mm3 (diameter; 10 mm). The mock-infected orthotopic primary tumor grew rapidly. After i.t. OBP-401 injection, the growth of the orthotopic tumors was arrested. Six weeks after implantation, the fluorescent area and fluorescence intensity showed no increase from the beginning of treatment. OBP-401 was then injected into high-metastatic MDA-MB-231-RFP primary orthotopic tumor growing in mice which already had developed metastasis within lymphatic ducts. All 7 of 7 control mice subsequently developed lymph node metastasis. In contrast, none of 7 mice which received OBP-401 had lymph node metastasis. Seven of 7 control mice also had gross lung metastasis. In contrast, none of the 7 mice which received OBP-401 had gross lung metastasis. Confocal laser microscopy imaging demonstrated that all control mice had diffuse lung metastases. In contrast, all 7 mice which received OBP-401 only had a few metastatic cells in the lung. OBP-401 treatment significantly extended survival of the treated mice.
- Published
- 2016