Development of a DNA vaccine targeting Merkel cell polyomavirus.
Merkel cell carcinoma (MCC) is a rare but devastating skin disease that is increasing in incidence within the United States. The poor prognosis of MCC patients and limited understanding of MCC pathogenesis warrants innovative treatments to control MCC. Several lines of evidence have pointed to Merkel cell polyomavirus (MCPyV) as the etiological agent of MCC. In particular, the amino terminus of MCPyV large T antigen (LT) (aa1-258) is expressed in all MCPyV-positive tumors and plays an important role in MCC oncogenesis, rendering it an ideal therapeutic target for vaccination. In the current study, we developed a DNA vaccine encoding MCPyV LT aa1-258 (pcDNA3-LT). Within our pcDNA3-LT DNA vaccine, we identified that MCPyV LT aa136-160 likely contains an LT-specific CD4+ T helper epitope. We have also created an LT-expressing B16/LT tumor model using B16, a murine melanoma cell line, to characterize the potency of our DNA vaccine. Using this tumorigenic B16/LT tumor model, we found that pcDNA3-LT DNA vaccine generates antitumor effects mainly mediated by CD4+ T cells against B16/LT tumors in vaccinated C57BL/6 mice. Thus, immunotherapy using pcDNA3-LT DNA vaccine may represent a promising approach for the control of MCPyV-associated lesions. The B16/LT tumor model further serves as a useful model for testing various vaccine strategies against MCC.
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.
Qi
Q
Zeng
Bianca P
BP
Gomez
Raphael P
RP
Viscidi
Shiwen
S
Peng
Liangmei
L
He
Barbara
B
Ma
T-C
TC
Wu
Chien-Fu
CF
Hung
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000276:immunology; D000957:Antigens, Viral, Tumor / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004279:DNA, Viral / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007273:Injections, Intramuscular; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology / Q000628:therapy; D059965:Merkel cell polyomavirus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D027601:Polyomavirus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology* / Q000627:therapeutic use; D014765:Viral Vaccines / Q000276:immunology* / Q000627:therapeutic use
D000952:Antigens, Polyomavirus Transforming; D000957:Antigens, Viral, Tumor; D004279:DNA, Viral; D019444:Vaccines, DNA; D014765:Viral Vaccines