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Published in: Cancer Immunology, Immunotherapy 12/2006

01-12-2006 | Original Article

Identification of a new HLA-A*0201-restricted cytotoxic T lymphocyte epitope from CML28

Published in: Cancer Immunology, Immunotherapy | Issue 12/2006

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Abstract

Identification of cytotoxic T lymphocyte (CTL) epitopes from additional tumor antigens is essential for the development of specific immunotherapy of malignant tumors. CML28, a recently discovered cancer-testis (CT) antigen from chronic myelogenous leukemia, is considered to be a promising target of tumor-specific immunotherapy. Because HLA-A*0201 is one of the most common histocompatibility molecule in Chinese, we aim at identifying CML28 peptides presented by HLA-A*0201. A panel of CML28-derived antigenic peptides was predicted using a computer-based program. Four peptides with highest predicted score were synthesized and tested for their binding affinities to HLA-A*0201 molecule. Then these peptides were assessed for their immunogenicity to elicit specific immune responses mediated by CTLs both in vitro, from PBMCs sourced from four healthy HLA-A*0201+ donors, and in vivo, in HLA-A*0201 transgenic mice. One of the tested peptides, CML28(173–181), induced peptide-specific CTLs in vitro as well as in vivo, which could specifically secrete IFN-γ and lyse major histocompatibility complex (MHC)-matched tumor cell lines endogenously expressing CML28 antigen and CML28(173–181) pulsed Jurkat-A2/Kb cells, respectively. These results demonstrate that CML28(173–181) is a naturally processed and presented CTL epitope with HLA-A*0201 motif and has a promising immunogenicity both in vitro and in vivo. As CML28 is expressed in a large variety of histological tumors besides chronic myelogenous leukemia, we propose that the newly identified epitope, CML28(173–181), would be of potential use in peptide-based, cancer-specific immunotherapy against a broad spectrum of tumors.
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Metadata
Title
Identification of a new HLA-A*0201-restricted cytotoxic T lymphocyte epitope from CML28
Publication date
01-12-2006
Published in
Cancer Immunology, Immunotherapy / Issue 12/2006
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-006-0152-8

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