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OBP-401-GFP telomerase-dependent adenovirus illuminates and kills high-metastatic more effectively than low-metastatic triple-negative breast cancer in vitro

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Abstract

We previously described the development of a highly-invasive, triple-negative breast cancer (TNBC) variant using serial orthotopic implantation of MDA-MB-231 human breast cancer in nude mice. The isolated variant is highly invasive in the mammary gland and metastasized to lymph nodes in 10 of 12 mice compared with 2 of 12 of the parental cell line. OBP-401 is a telomerase-dependent cancer-specific, green fluorescent protein (GFP)-expressing adenovirus. OBP-401 was used to infect parental MDA-MB-231P cells and high-metastatic MDA-MB-231H and MDA-MB-231HLN isolated from a lymph node metastasis and MDA-MB-231HLM isolated from a lung metastasis. Time-course imaging showed that OBP-401 labeled MDA-MB-231HP, MDA-MB-231HLN, and MDA-MB-231HLM cells more brightly than MDA-MB-231 parental cells. OBP-401 killed MDA-MB-231H, MDA-MB-231HLN, and MDA-MB-231HLM cells more efficiently than MDA-MB-231P parental cells. These results indicate that OBP-401 could infect, label and then kill high-metastatic MDA-MB-231 more efficiently than low-metastatic MDA-MB-231.

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Acknowledgements

This study was supported in part by the National Cancer Institute grants CA 132971 and CA142669. This study was also supported in part by grants from the Ministry of Health, Labour, and Welfare, Japan (to T Fujiwara; No. 10103827, No. 13801426 and No. 14525167) and grants from the Ministry of Education, Culture, Sports, Science and Technology, Japan (to T Fujiwara; No. 25293283).

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Correspondence to T Fujiwara or R M Hoffman.

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Competing interests

YU is the President & CEO of Oncolys BioPharma, Inc., the manufacturer of OBP-401 (Telomescan). HT and TF are consultants of Oncolys BioPharma, Inc. The remaining authors declare no conflict of interest.

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This paper is dedicated to the memory of A.R. Moossa, MD, and Sun Lee, MD.

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Yano, S., Takehara, K., Kishimoto, H. et al. OBP-401-GFP telomerase-dependent adenovirus illuminates and kills high-metastatic more effectively than low-metastatic triple-negative breast cancer in vitro. Cancer Gene Ther 24, 45–47 (2017). https://doi.org/10.1038/cgt.2016.67

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