Effective priming of cytotoxic T lymphocyte precursors by subcutaneous administration of peptide antigens in liposomes accompanied by anti-CD40 and anti-CTLA-4 antibodies

Recently it has been shown that modulation of CD40 molecules on antigen (Ag ) carrying dendritic cells (DC) can bypass T cell help, resulting in primin g cytotoxic T lymphocytes (CTL) specific for the Ag. In the present study w e attempted to prime peptide Ag-specific CTL by a new method in which a pep tide Ag in liposome (liposomal peptide), consisting of phosphatidylserine a nd phosphatidylcholine (3:7), was administrated subcutaneously with anti-CD 40 and/or CTLA-4 monoclonal antibodies (mAb) to mice. We found that the sub cutaneous administration of the liposomal peptide with both anti-CD40 and a nti-CTLA-4 mAb enhanced CTL responses comparing with those induced by the l iposomal peptide alone or the liposomal peptide plus each mAb. It was shown that liposomes were critical for induction of the CTL activity. Flow cytom etry analysis of a peptide-hearing DC in lymph nodes (LN) and measurement o f serum IL-12 indicated that anti-CD40 mAb promoted migration of DC to the LN, where DC might differentiate and acquire ability of priming CTL. These findings provide a possibility that our procedure is applicable to cancer p atients.