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

doi:10.1016/j.cellimm.2008.01.001

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

Department of Microbiology and Molecular Genetics

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	24-30
Number of pages	7
Journal	Cellular Immunology
Volume	250
Issue number	1-2
DOIs	https://doi.org/10.1016/j.cellimm.2008.01.001
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cellimm.2008.01.001

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title = "A melanoma multiepitope polypeptide induces specific CD8+ T-cell response",

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.",

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AU - Margalit, Hanna

AU - Peretz, Tamar

AU - Golenser, Jacob

AU - Lotem, Michal

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AB - 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.

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

Abstract

Bibliographical note

Keywords

UN SDGs

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