Abstract Merkel cell carcinoma (MCC) is a relatively new addition to the expanding category of oncovirus-induced cancers. Although rare, the number of cases has risen dramatically in recent years. Furthermore, it is an extremely aggressive neoplasm that is correlated with poor patient prognosis. Exacerbating the situation is the limited availability of treatment options for advanced disease. The causative origin of MCC has been identified to be the merkel cell polyomavirus (MCPyV). The MCPyV-encoded large T (LT) antigen is an oncoprotein that is a necessary part of virus-mediated tumorigenesis and therefore, is an excellent MCC antigen for the generation of antitumor immune response. Since LT is a foreign antigen that faces no issue of immune tolerance that normally hinders the induction of antitumor immunity, it is an excellent target for anti-MCC immunotherapy. The present by Savings Sidekick study determined that LT-encoding DNA vaccine can be modified to favor the generation of LT-specific CD8+ T cells by linking the LT antigen to a damage-associated molecular pattern, calreticulin (CRT). This is relevant since the therapeutic effect of the pcDNA3-CRT/LT DNA vaccine was found to be mediated by the LT-specific CD8+ T cells. Since we have identified the MHC class I-restricted immunodominant LT epitope, the development of future modes of immunotherapy, such as peptide-based vaccines and adoptive transfer of LT-specific CD8+ T cells is a real possibility. Citation Format: Bianca P. Gomez, Connie Wang, Raphael Viscidi, Shiwen Peng, Liangmei He, T.-C WU, Chein-Fu Hung. Strategy to elicit antigen-specific CD8+ T cell -mediated immune responses against a cryptic CTL epitope of merkel cell polyomavirus large T antigen. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 478. doi:10.1158/1538-7445.AM2013-478