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

Lookup NU author(s): Professor Anne Dickinson

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Abstract

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--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.

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Author(s): Al Qudaihi G, Lehe C, Negash M, Al-Alwan M, Ghebeh H, Mohamed SY, Saleh AJM, Al-Humaidan H, Tbakhi A, Dickinson A, Aljurf M, Dermime S

Publication type: Article

Publication status: Published

Journal: Leukemia & Lymphoma

Year: 2009

Volume: 50

Issue: 2

Pages: 260-269

Print publication date: 01/01/2009

ISSN (print): 1042-8194

ISSN (electronic): 1029-2403

Publisher: Taylor & Francis Ltd.

URL: http://dx.doi.org/10.1080/10428190802578478

DOI: 10.1080/10428190802578478

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