Lipopeptide-based melanoma cancer vaccine induced a strong MART-27-35-cytotoxic T lymphocyte response in a preclinal study.
Identification of tumor antigens and their optimal antigenic peptides raised hopes for the development of peptide-based immunotherapeutic vaccine strategies for human melanoma, however. Synthetic peptides alone are not immunogenic enough, and adequate formulation is critical for elaboration of peptide vaccines. To improve formulation, we evaluated 2 lipopeptide constructs, both including HLA-A2-restricted MART 27-35-CD8+ T lymphocyte (CTL) epitope covalently linked to universal tetanus toxoid (TT) 830-843 helper T lymphocyte (HTL) epitope, in HLA-A2 transgenic mouse models that mimic human CTL responses in vivo. These 2 constructs only differed in the formulation of their lipid tail. We showed that lipopeptide constructs were strongly recognized, in vitro, by human MART 27-35 cytotoxic T cells derived from tumor-infiltrating lymphocytes. The transgenic Mice immunized with these 2 MART lipopeptide formulations containing covalently linked HTL-CTL epitopes induced strong MART 27-35 cytotoxic T cells. This CTL induction was critically dependent on the presence of the helper T lymphocyte epitope. These results also showed that a single palmitoyl-lysine chain is enough to assure immunogenicity of a given peptide and that the presence of a lipid tail bypass the need for adjuvant. These results support the selection of MART-lipopeptide melanoma vaccine for evaluation in a clinical trial.
Le Gal
Frédérique-Anne
FA
Laboratoire d'Immunologie des Pathologies Infectieuses et Tumorales, INSERM unité 445, I.C.G.M., Université R.Descartes, Hôpital Cochin, Paris, France.
Prevost-Blondel
Armelle
A
Lengagne
Renée
R
Bossus
Marc
M
Farace
Françoise
F
Chaboissier
Aude
A
Gras-Masse
Hélène
H
Engelhard
Victor H
VH
Guillet
Jean-Gérard
JG
Gahéry-Ségard
Hanne
H
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000235:genetics; D008074:Lipoproteins / Q000737:chemistry / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000737:chemistry / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D000939:Epitopes; D015789:HLA-A2 Antigen; D008074:Lipoproteins; C105787:MART-1-Melan-A(27-35) epitope; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D013745:Tetanus Toxoid; C093151:tetanus toxoid (830-843)