Creation of a Merkel cell polyomavirus small T antigen-expressing murine tumor model and a DNA vaccine targeting small T antigen

Cell & Bioscience

Chien-Fu Hung²  Raphael P Viscidi⁴  T-C Wu³  Ya Chea Tsai¹  Liangmei He¹  Bianca Gomez¹ 

[1] Departments of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA;Departments of Pathology and Oncology, The Johns Hopkins University School of Medicine, CRB II Room 307, 1550 Orleans Street, Baltimore, MD 21231, USA;Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA;Pediatrics, Johns Hopkins Medical Institutions, Baltimore, MD, USA

关键词: Merkel cell carcinoma;    Small T antigen;    Merkel cell polyomavirus;    Gene therapy;    DNA vaccine;   

Others  :  791592
DOI  :  10.1186/2045-3701-3-29

 received in 2013-02-12, accepted in 2013-05-24,  发布年份 2013

【 摘 要 】

Background

Merkel cell polyomavirus (MCPyV) is a DNA virus expressing transcripts similar to the large T (LT) and small T (ST) transcripts of SV40, which has been implicated in the pathogenesis of Merkel cell carcinoma (MCC), a rare and highly aggressive neuroendocrine skin cancer. MCPyV LT antigen expression was found to be a requirement for MCC tumor maintenance and ST protein also likely contributes to the carcinogenesis of MCC. Previously, we have identified the probable immunodominant epitope of MCPyV LT and developed a DNA vaccine encoding this epitope linked to calreticulin. The LT-targeting DNA vaccine generated prolonged survival, decreased tumor size and increased LT-specific CD8+ T cells in tumor-bearing mice.

Results

In this study, we developed a MCPyV ST-expressing tumor cell line from B16 mouse melanoma cells. We then utilized this ST-expressing tumor cell line to test the efficacy of a DNA vaccine encoding ST. In ST-expressing tumor-bearing mice, this vaccine, pcDNA3-MCC/ST, generated a significant number of ST antigenic peptide-specific CD8+ T cells and experienced markedly enhanced survival compared to mice vaccinated with empty vector.

Conclusions

The formation of an effective vaccine against MCPyV has the potential to advance the field of MCC therapy and may contribute to the control of this severe malignancy through immunotherapy. Both of the innovative technologies presented here provide opportunities to develop and test MCPyV-targeted therapies for the control of Merkel cell carcinoma.

【 授权许可】

   
2013 Gomez et al.; licensee BioMed Central Ltd.

【 图 表 】

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