Efficient induction of tumoricidal cytotoxic T lymphocytes by HLA-A0201 restricted, melanoma associated, L(27)Melan-A/MART-1(26-35) peptide encapsulated into virosomes in vitro

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...

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Bibliographic Details
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
Subjects:
Adjuvants, Immunologic
Cells, Cultured
Cytotoxicity, Immunologic
Drug Delivery Systems
Epitopes - administration & dosage
Epitopes - immunology
HLA-A Antigens - immunology
HLA-A2 Antigen
Humans
Influenza A virus - immunology
Influenza Vaccines - immunology
Lymphocytes, Tumor-Infiltrating - immunology
Lymphocytes, Tumor-Infiltrating - pathology
Neoplasm Proteins - administration & dosage
Neoplasm Proteins - immunology
T-Lymphocytes, Cytotoxic - immunology
Vaccines, Synthetic - administration & dosage
Virosomes - administration & dosage
Virosomes - immunology
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Summary: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 L(27)Melan-A/Mart-1(26-35) HLA-A0201 restricted 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 L(27)Melan-A/Mart-1(26-35) specific CTL, as compared to soluble peptides, in particular at low nominal epitope concentrations (
ISSN:0264-410X
DOI:10.1016/j.vaccine.2005.07.099