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Blood, 1 October 2008, Vol. 112, No. 7, pp. 2956-2964. Prepublished online as a Blood First Edition Paper on May 23, 2008; DOI 10.1182/blood-2008-02-137695. This Article Full Text (PDF) All Versions of this Article: blood-2008-02-137695v1 112/7/2956    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chaise, C. Articles by Stevenson, F. K. Search for Related Content PubMed PubMed Citation Articles by Chaise, C. Articles by Stevenson, F. K. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 6, 2008 Accepted May 3, 2008 DNA VACCINATION INDUCES WT1-SPECIFIC T-CELL RESPONSES WITH POTENTIAL CLINICAL RELEVANCE Coralie Chaise, Sarah L Buchan, Jason Rice, Jeanine Marquet, Helene Rouard, Mathieu Kuentz, Gisella E Vittes, Valerie Molinier-Frenkel, Jean-Pierre Farcet, Hans J. Stauss, Marie-Helene Delfau-Larue, and Freda K. Stevenson* Departement d'Immunologie, dermatologie et Oncologie, IMRB, Paris, France Genetic Vaccine Group, Cancer Sciences Division, Southampton University Hospitals, Southampton, United Kingdom Faculte de Medicine, Universite de Paris 12, Paris, France Laboratoire de Therapie Cellulaire, EFS, Paris, France Servive d'Hematologie, AP-HP, Hopital Henri Mondor, Paris, France Service d'Immunologie, AP-HP, Hopital Henri Mondor, Paris, France Department of Immunology and Molecular Pathology, Royal Free Hospital, London, United Kingdom * Corresponding author; email: fs{at}soton.ac.uk. The Wilms' tumor antigen, WT1, is associated with several human cancers including leukemia. We have evaluated WT1 as an immunotherapeutic target using our proven DNA fusion vaccine design, p.DOM-peptide, encoding a minimal tumor-derived MHC class I-binding epitope downstream of a foreign sequence (DOM) of tetanus toxin. Three p.DOM-peptide vaccines, each encoding a different WT1-derived, HLA-A2-restricted epitope, induced cytotoxic T lymphocytes (CTL) in humanized transgenic mice expressing chimeric HLA-A2, without affecting hematopoietic stem cells. Mouse CTL killed human leukemia cells in vitro indicating peptide processing/presentation. Low numbers of T cells specific for these epitopes have been described in cancer patients. Expanded human T cells specific for each of the three epitopes were lytic in vitro. Focussing on human WT137-45-specific cells, the most avid of the murine responses, we demonstrated lysis of primary leukemias, underscoring their clinical relevance. Finally we showed that these human CTL kill target cells transfected with the relevant p.DOM-peptide DNA vaccine, confirming that WT1-derived epitopes are presented to T cells similarly by tumors and following DNA vaccination. Together, these data link mouse and human studies to suggest that rationally-designed DNA vaccines encoding WT1-derived epitopes, particularly WT137-45, have the potential to induce/expand functional tumor-specific cytotoxic responses in cancer patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Expectation for DNA leukemia vaccines Haruo Sugiyama Blood 2008 112: 2602. [Full Text] [PDF] This article has been cited by other articles: T. R. Hercus, D. Thomas, M. A. Guthridge, P. G. Ekert, J. King-Scott, M. W. Parker, and A. F. Lopez The granulocyte-macrophage colony-stimulating factor receptor: linking its structure to cell signaling and its role in disease Blood, August 13, 2009; 114(7): 1289 - 1298. [Abstract] [Full Text] [PDF]

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