Enhancement of lytic activity of leukemic cells by CD8+ cytotoxic T lymphocytes generated against a WT1 peptide analogue

The Wilms tumor antigen 1 (WT1) antigen is over-expressed in human leukemias, making it an attractive target for immunotherapy. Most WT1-specific Cytotoxic T Lymphocytes (CTLs) described so far displayed low avidity, limiting its function. To improve the immunogenicity of CTL epitopes, we replaced t...

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Bibliographic Details
Published in:	Leukemia & lymphoma Vol. 50; no. 2; pp. 260 - 269
Main Authors:	Al Qudaihi, Ghofran, Lehe, Cynthia, Negash, Muna, Al-Alwan, Monther, Ghebeh, Hazem, Mohamed, Said Yousuf, Saleh, Abu-Jafar Mohammed, Al-Humaidan, Hind, Tbakhi, Abdelghani, Dickinson, Anne, Aljurf, Mahmoud, Dermime, Said
Format:	Journal Article
Language:	English
Published:	United States Informa UK Ltd 01-01-2009 Taylor & Francis
Subjects:	AML Biomimetic Materials - metabolism CD8+ CTL Cell Line, Tumor dendritic cells Epitopes - immunology HLA-A Antigens - immunology HLA-A Antigens - metabolism HLA-A2 Antigen Humans immunotherapy Interferon-gamma - biosynthesis Leukemia - immunology Leukemia - metabolism Leukemia - pathology Peptide Fragments - genetics Peptide Fragments - immunology Peptide Fragments - metabolism peptide modification Protein Binding T-Lymphocytes, Cytotoxic - drug effects T-Lymphocytes, Cytotoxic - immunology WT1 Db126 analogue WT1 Proteins - genetics WT1 Proteins - immunology WT1 Proteins - metabolism
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Summary:	The Wilms tumor antigen 1 (WT1) antigen is over-expressed in human leukemias, making it an attractive target for immunotherapy. Most WT1-specific Cytotoxic T Lymphocytes (CTLs) described so far displayed low avidity, limiting its function. To improve the immunogenicity of CTL epitopes, we replaced the first-amino-acid of two known immunogenic WT1-peptides (126 and 187) with a tyrosine. This modification enhances 126Y analogue-binding ability, triggers significant number of IFN-γ-producing T cells (P = 0.0003), induces CTL that cross-react with the wild-type peptide, exerts a significant lytic activity against peptide-loaded-targets (P = 0.0006) and HLA-A0201-matched-leukemic cells (P = 0.0014). These data support peptide modification as a feasible approach for the development of a leukemia-vaccine.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1042-8194 1029-2403
DOI:	10.1080/10428190802578478