The use of synthetic peptides derived from tumor-associated Ags is attractive for the development of antitumoral vaccines as far as strong adjuvants are found to render them immunogenic. Here, we investigated the possibility to enhance the CD8 response against the human and mouse shared TERT(572Y) HLA-A*0201 restricted modified cryptic peptide by using ODN-CpG as adjuvant. Humanized transgenic mice were immunized with the TERT(572Y) modified cryptic peptide in the presence of ODN-CpG and compared to mice immunized in IFA. By contrast with IFA, we first showed that, in vivo, ODN-CpG leads to the recruitment of dendritic cells in the lymph nodes draining the injection site. Those cells and especially the CD11c+ CD11b- CD8a+ lymphoid and the CD11c+ B220+ plasmacytoid dendritic cells were activated as shown by up-regulation of CD40 at their cell surface. Immunization against TERT(572Y) peptide in the presence of ODN-CpG rather than IFA led to a strong CD8 response and can delayed mortality in an induced tumor model. Study of the CD8 response obtained after antigenic challenge suggested that a functional memory response is induced upon vaccination with ODN-CpG. Thus, MHC class I-restricted epitope in combination of ODN-CpG is a promising and rather simple cancer vaccine formulation.