A melanoma multiepitope polypeptide induces specific CD8+ T-cell response

Adva Levy, Jacob Pitcovski, Shoshana Frankenburg*, Orit Elias, Yael Altuvia, Hanna Margalit, Tamar Peretz, Jacob Golenser, Michal Lotem

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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-γ 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.

Original languageAmerican English
Pages (from-to)24-30
Number of pages7
JournalCellular Immunology
Volume250
Issue number1-2
DOIs
StatePublished - Nov 2007

Bibliographical note

Funding Information:
This work was supported by NIH Grant 1 R21 CA114160-01A1 (to S.F.), by the Israel Ministry of Commerce, and by the Chief Scientist of the Israel Ministry of Health. Several of the T-cell lines used were kindly provided by the Surgery Branch, NCI, NIH.

Keywords

  • Cytotoxic T cells
  • Melanoma
  • Multiepitope

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