%0 Journal Article
%T Strategy for eliciting antigen-specific CD8+ T cell-mediated immune response against a cryptic CTL epitope of merkel cell polyomavirus large T antigen
%A Bianca P Gomez
%A Connie Wang
%A Raphael P Viscidi
%A Shiwen Peng
%A Liangmei He
%A T-C Wu
%A Chien-Fu Hung
%J Cell & Bioscience
%D 2012
%I BioMed Central
%R 10.1186/2045-3701-2-36
%X The present study shows that DNA vaccine-induced generation of LT-specific CD8+ T cells is augmented by linking CRT to the LT antigen. This is relevant since the therapeutic effects of the pcDNA3-CRT/LT DNA vaccine is mediated by LT-specific CD8+ T cells. Mice vaccinated with the DNA vaccine produced demonstrably more LT-specific CD8+ T cells. The DNA vaccine was also able to confer LT-specific CD8+ T cell-mediated protective and therapeutic effects to prolong the survival of mice with LT-expressing tumors. In the interest of determining the LT epitope which most MCC-specific CD8+ T cells recognize, we identified the amino acid sequence of the immunodominant LT epitope as aa19-27 (IAPNCYGNI) and found that it is H-2kb-restricted.The results of this study can facilitate the development of other modes of MCC treatment such as peptide-based vaccines and adoptive transfer of LT-specific CD8+ T cells. Likewise, the MCC DNA vaccine has great potential for clinical translation as the immunologic specificity is high and the treatment strategy can be exported to address other virus-induced tumors.While historically uncommon, merkel cell carcinoma (MCC) incidence has risen steadily over recent years [1,2]. MCC is a cutaneous neoplasm that originates from the mechanoreceptor merkel cells, which are derived from the embryonic neural crest. Highly malignant, this disease is prone to metastasis, and therefore afflicted patients have unfavorable prognosis and high mortality rates. MCC is among the most aggressive of skin cancers with patient mortality greater than that of melanoma [3]. Most often, MCC sufferers are seniors, immunosuppressed post-transplant patients, and immunodeficient individuals [4]; with the disease first appearing at sun-exposed areas such as the head and neck [5].Investigation into the contributing factors that lead to MCC development has determined a possible infectious origin for the disease, specifically, the merkel cell polyomavirus (MCPyV) [6]. Studies t
%K DNA vaccine
%K Gene therapy
%K Merkel cell polyomavirus
%K Cryptic CTL Epitope
%K Large T antigen
%U http://www.cellandbioscience.com/content/2/1/36