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 lymp hocytes (CTL) that recognize tumor-associated antigen. It is: generally acc epted that CTL responses are induced when antigen is delivered into the cyt osol. The pi-I-sensitive liposomes as vehicles are well known for their cap acity to deliver the antigen into the cytosol. In this work, immunization o f mice with CTL epitope peptides from Hantaan nucleocapsid protein (M6) or human papilloma virus E7 encapsulated in pH-sensitive liposomes induced eff ective antigen-specific CTL responses. The CTL responses induced by M6 pept ide encapsulated in pH-sensitive: liposomes blocked the formation of tumor mass from Hantaan NP transfected B16 melanoma cells in C57BL/6 mice and del ayed 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. (C) 2001 Elsevier Science Ltd. All rights reserved.