Research article summary (published 13 Nov 2009):

The shared tumor associated antigen cyclin-A2 is recognized by high-avidity T-cells.

Full Abstract

Cyclin-A2, a key cell cycle regulator, has been shown to be overexpressed in various types of malignancies with little expression in normal tissue. Such tumor-associated genes potentially are useful targets for cancer immunotherapy. However, high-avidity cyclin-specific T cells are considered to be thymically deleted. We identified at least one nonameric HLA-A*0201 binding cyclin-A2 epitope by a reverse immunology approach. Using a highly efficient T-cell expansion system that is based on CD40-activated B (CD40-B) cells as sole antigen-presenting cells we successfully generated cyclin-A2 specific CTL from HLA-A*0201(+) donors. Interestingly, high-avidity cyclin-A2 specific CTL lines, which recognized peptide-pulsed and antigen expressing target cells, were indeed generated by stimulation with CD40-B cells when pulsed with low concentrations of peptide, whereas CD40-B cells pulsed at saturating concentrations could only induce low-avidity CTL, which recognized peptide-pulsed target cells only. One high-avidity CTL line was subcloned and CTL clones, whose peptide concentration required for half-maximal lysis were less than 1 nM, could lyse cyclin-A2 expressing tumor cells. Taken together, cyclin A2 is an attractive candidate for immune intervention in a significant number of cancer patients and high-avidity T cells can be readily generated using CD40-B cells as antigen-presenting cells.

Author information

Author/s: Kondo, Eisei (E); Maecker, Britta (B); Draube, Andreas (A); Klein-Gonzalez, Nela (N); Shimabukuro-Vornhagen, Alexander (A); Schultze, Joachim L (JL); von Bergwelt-Baildon, Michael S (MS);

Affiliation: Max Eder Junior Research Group, Clinic I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: International journal of cancer. Journal international du cancer (Int J Cancer), published in United States. (Language: eng)

Reference: 2009-Nov; vol 125 (issue 10) : pp 2474-8

Dates: Created 2009/09/28; Completed 2009/11/05;

PMID: 19681121, status: MEDLINE (last retrieval date: 11/5/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Antigens, CD40 - immunology; metabolism Antigens, Neoplasm - immunology; metabolism B-Lymphocytes - immunology; metabolism Cyclin A - immunology; metabolism Epitopes - immunology; metabolism HLA-A Antigens - immunology; metabolism Humans

Interferon-gamma - metabolism Neoplasms - immunology; metabolism; pathology Peptide Fragments - immunology; metabolism Protein Binding T-Lymphocytes - immunology; metabolism T-Lymphocytes, Cytotoxic - immunology Tumor Cells, Cultured

Associated Chemicals: Antigens, CD40 (0) ; Antigens, Neoplasm (0) ; CCNA2 protein, human (0) ; Cyclin A (0) ; Epitopes (0) ; HLA-A Antigens (0) ; HLA-A*0201 antigen (0) ; Peptide Fragments (0) ; Interferon-gamma (82115-62-6)

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