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 ORCID: https://orcid.org/0000-0001-9416-2737, 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:	06 Nov 2022 13:24
URI:	https://orca.cardiff.ac.uk/id/eprint/26913

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