Efficient induction of tumoricidal cytotoxic T lymphocytes by HLA-A0201 restricted, melanoma associated, L27Melan-A/MART-126–35 peptide encapsulated into virosomes in vitro

• Published in: Vaccine 2005-12, Vol.23 (48-49), p.5572-5582
• Main Authors: Schumacher, Reto, Amacker, Mario, Neuhaus, Danielle, Rosenthal, Rachel, Groeper, Célia, Heberer, Michael, Spagnoli, Giulio C., Zurbriggen, Rinaldo, Adamina, Michel
• Format: Article
• Language: English
• ISSN: 0264-410X
• DOI: 10.1016/j.vaccine.2005.07.099

Cancer immunotherapy requires the induction of HLA class I restricted cytotoxic T lymphocytes (CTL) specific for tumor associated antigens (TAA). While a number of TAA have been identified, there is an urgent need for the development of adjuvants capable of stimulating CTL responsiveness. Previously, we reported the capacity of immunopotentiating reconstituted influenza virosomes (IRIV) to enhance CTL responses specific for synthetic peptides simultaneously added to cultures in soluble form. This effect was based on IRIV mediated activation of CD4+ T cells. Here we investigated the "in vitro" immunogenicity of a novel virosome formulation coupling in a single reagent the adjuvant power of IRIV to the capacity of liposomes to efficiently encapsulate synthetic peptides. As a model epitope we chose L27Melan-A/Mart-126-35 HLA-A0201restricted peptide from a melanoma-associated antigen widely used in tumor immunotherapy. The reagent thus developed induced the proliferation of CD4+ T cells characterized by a T helper 1 cytokine profile and CXCR3 expression. Most importantly, it significantly enhanced the generation of L27Melan-A/Mart-126-35 specific CTL, as compared to soluble peptides, in particular at low nominal epitope concentrations (