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Peptide vaccination elicits leukemia-associated antigen-specific cytotoxic CD8+ T-cell responses in patients with chronic lymphocytic leukemia

Giannopoulos, K., Dmoszynska, A., Kowal, M., Rolinski, J., Gostick, Emma, Price, David, Greiner, J., Rojewski, M., Stilgenbauer, S., Döhner, H. and Schmitt, M. 2010. Peptide vaccination elicits leukemia-associated antigen-specific cytotoxic CD8+ T-cell responses in patients with chronic lymphocytic leukemia. Leukemia 24 (4) , pp. 798-805. 10.1038/leu.2010.29

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Abstract

The receptor for hyaluronic acid-mediated motility (RHAMM) is a tumor-associated antigen in chronic lymphocytic leukemia (CLL). CD8+ T cells primed with the RHAMM-derived epitope R3, which is restricted by human leukocyte antigen (HLA)-A2, effectively lyse RHAMM+ CLL cells. Therefore, we initiated a phase I clinical trial of R3 peptide vaccination. Six HLA-A2+ CLL patients were vaccinated four times at biweekly intervals with the R3 peptide (ILSLELMKL; 300 μg per dose) emulsified in incomplete Freund's adjuvant; granulocyte-macrophage colony stimulating factor (100 μg per dose) was administered concomitantly. Detailed immunological analyses were conducted throughout the course of peptide vaccination. No severe adverse events greater than CTC I° skin toxicity were observed. Four patients exhibited reduced white blood cell counts during vaccination. In five of six patients, R3-specific CD8+ T cells were detected with the corresponding peptide/HLA-A2 tetrameric complex; these populations were verified functionally in four of five patients using enzyme-linked immunosorbent spot (ELISpot) assays. In patients with clinical responses, we found increased frequencies of R3-specific CD8+ T cells that expressed high levels of CD107a and produced both interferon-γ and granzyme B in response to antigen challenge. Interestingly, vaccination was also associated with the induction of regulatory T cells in four patients. Thus peptide vaccination in six CLL patients was safe and could elicit to some extent specific CD8+ T-cell responses against the tumor antigen RHAMM.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords: tumor immunity; vaccination; CLL; leukemia-associated antigen; receptor for hyaluronic acid-mediated motility (RHAMM/CD168)
Publisher: Nature Publishing Group
ISSN: 0887-6924
Last Modified: 08 Mar 2019 22:43
URI: http://orca.cf.ac.uk/id/eprint/26913

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