A Novel Recombinant Multi-Epitope Vaccine Could Induce Specific Cytotoxic T Lymphocyte Response In Vitro and In Vivo

Cytotoxic CD8+ T lymphocytes (CTLs) play an important role in killing tumor cells. To develop therapeutic vaccines that can induce specific immune response, we designed a novel recombinant multiepitope vaccine YL66 which consists of HLA-A2-restricted CTL epitopes from two widely expressed tumor antigen cyclooxygenase-2 and MAGE-4, linked with membrane permeable Tat-PTD and the universal T helper epitope. The DNA fragment of YL66 was cloned into pGEX-4T-2-YL66 and pcDNA3.1(+)-YL66, respectively. Then, we tested whether the expressed protein GST-YL66 and DNA vaccine pcDNA3.1(+)-YL66 has the ability to induce CTL response both in vitro (from human peripheral blood mononuclear cells (PBMCs) of HLA-A*02+ healthy donors) and in vivo (in HLA-A2.1/Kb transgenic(Tg) mice). The results showed that the CTLs induced by protein GST-YL66 and DNA vaccine pcDNA3.1(+)-YL66 could lysis tumor cells and release IFN-γ both in vitro and in vivo, indicating that the multiepitope YL66 could be used as a novel vaccine against patients with tumors expressing COX-2 and/or MAGE-4.