A melanoma multiepitope polypeptide induces specific CD8+ T-cell response.
Strategies using epitope-based vaccination are being considered for melanoma immunotherapy, in an attempt to overcome failure of other modalities. In the present study, we designed and produced a multiepitope polypeptide for melanoma (MEP-mel), which contains three repeats of four antigenic epitopes (gp100: 209-217 (210M); gp100: 280-288 (288V); Mart1: 26-35 (27L); tyrosinase: 368-376 (370D). The peptides were attached to each other by linkers containing sequences recognized by the proteasome, to improve protein cleavage and antigen presentation. The results show that peptide-specific T cells produced IFN-gamma when stimulated with MEP-mel-transfected dendritic cells. The presentation of peptides by MEP-mel-transfected dendritic cells was proteasome-dependent and was more long-lasting than the presentation of exogenously delivered native peptides. When dendritic cells were loaded with MEP-mel protein, weak cross presentation was induced. The production of multiepitope molecules based on several peptides linked by sequences sensitive to proteasomal cleavage represents a promising new tool for the improvement of cancer immunotherapy.
Levy
Adva
A
Migal, Kiryat Shmona, Israel.
Pitcovski
Jacob
J
Frankenburg
Shoshana
S
Elias
Orit
O
Altuvia
Yael
Y
Margalit
Hanna
H
Peretz
Tamar
T
Golenser
Jacob
J
Lotem
Michal
M
D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002469:Cell Separation; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics / Q000493:pharmacokinetics; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D015195:Drug Design; D018274:Electroporation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D004925:Escherichia / Q000235:genetics; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000276:immunology*; D010455:Peptides / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011506:Proteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology
D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D018984:Epitopes, T-Lymphocyte; C528902:MEP-mel protein; D010455:Peptides; D061988:Proteasome Inhibitors; D011506:Proteins; D007371:Interferon-gamma; D046988:Proteasome Endopeptidase Complex