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Research Article

Detection and preliminary characterization of CD8+T lymphocytes specific for Wilms’ tumor antigen in patients with non-Hodgkin lymphoma

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Pages 2490-2499 | Received 19 Nov 2012, Accepted 06 Mar 2013, Published online: 30 Apr 2013
 

Abstract

Wilms’ tumor antigen (WT1) is overexpressed in many different solid tumors and hematologic malignancies. However, little is known about WT1 expression or WT1-specific immune responses in patients with non-Hodgkin lymphoma (NHL). In a cross-sectional survey study, we investigated the immune recognition of WT1 by patients with NHL. Utilizing a WT1 overlapping peptide library, we discovered that a large percentage of patients with NHL of all grades maintain WT1-specific T cells. Ex vivo frequencies of these T cells measured from unfractionated samples by the CD137 activation marker assay were high in many patients (some > 1% CD8+). Using standard in vitro techniques we discovered that they were cytotoxic to WT1 peptide library-loaded T2 cells and WT1 antigen-primed autologous Epstein–Barr virus-transformed B cell lines (EBV-LCLs) and expressed interferon gamma (IFN-γ). In addition, we detected WT1 mRNA transcripts in diseased lymph node tissues of patients with NHL utilizing real-time quantitative polymerase chain reaction (RT-qPCR) technology. These results are the first example of strong T cell reactivity against WT1 in patients with NHL which also demonstrate strong cytotoxicity against peptide-loaded tumor cells. The potential for developing WT1 as a target for immunotherapy in NHL deserves further exploration.

Acknowledgements

The authors thank the staff of the Hematology/Hematopoietic Cell Transplant team for their constant support of the program. The dedication of the hematology nurse coordinators and their staff in facilitating the study, assisting the patients with informed consent and collecting the blood specimens is greatly appreciated. The authors are grateful to their valued patients for vital contributions to the study. They would also like to thank Edwin Manuel for helpful comments and Jessica Lo for technical assistance.

Potential conflict of interest:

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

This work was partially supported by the Tim Nesvig Lymphoma Fellowship and Research Fund (R.N. and D.J.D.) and by the ThinkCure Foundation (R.N. and D.J.D.), and PHS grants CA077544 (D.J.D.) and CA030206 (D.J.D. and S.J.F.). The City of Hope Cancer Center is supported by CA33572.

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