Development of Th1-mediated CD8+ effector T cells by vaccination with epitope peptides encapsulated in pH-sensitive liposomes.

There have been many studies for tumor therapy mediated by cytotoxic T lymphocytes (CTL) that recognize tumor-associated antigen. It is generally accepted that CTL responses are induced when antigen is delivered into the cytosol. The pH-sensitive liposomes as vehicles are well known for their capacity to deliver the antigen into the cytosol. In this work, immunization of mice with CTL epitope peptides from Hantaan nucleocapsid protein (M6) or human papilloma virus E7 encapsulated in pH-sensitive liposomes induced effective antigen-specific CTL responses. The CTL responses induced by M6 peptide encapsulated in pH-sensitive liposomes blocked the formation of tumor mass from Hantaan NP transfected B16 melanoma cells in C57BL/6 mice and delayed the growth of preinoculated melanoma cells. During the blockade of the tumor growth, the CTL response was maintained for at least approximately 6 weeks, and the mice secreted Th1 type cytokines such as IL-2 and IFN-gamma. These results suggested that the pH-sensitive liposomes might provide an effective peptide delivery system for CTL-mediated tumor therapy.