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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 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 Citation Map 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 CrossRef Google Scholar Articles by Chaise, C. Articles by Stevenson, F. K. PubMed PubMed Citation Articles by Chaise, C. Articles by Stevenson, F. K. Related Collections Immunobiology Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA DNA vaccination induces WT1-specific T-cell responses with potential clinical relevance Coralie Chaise1,2,*, Sarah L. Buchan3,*, Jason Rice3, Jeanine Marquet1,2, Hélène Rouard4, Mathieu Kuentz5, Gisella E. Vittes3, Valérie Molinier-Frenkel1,2,6, Jean-Pierre Farcet1,2,6, Hans J. Stauss7, Marie-Hélène Delfau-Larue1,2,6, and Freda K. Stevenson3 1 Inserm U-841, Institut Mondor de Recherche Biomédicale (IMRB), Département d'Immunologie, Dermatologie et Oncologie, Créteil, France; 2 Université Paris 12, Faculté de Médecine, Créteil, France; 3 Genetic Vaccine Group, Southampton University Hospitals Trust, Southampton, United Kingdom; 4 Laboratoire de Thérapie Cellulaire, Etablissement Français du Sang (EFS), Créteil, France; 5 Service d'Hématologie Clinique, and 6 Service d'Immunologie Biologique, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Henri Mondor, Créteil, France; and 7 Department of Immunology and Molecular Pathology, Royal Free Hospital, London, United Kingdom The Wilms tumor antigen, WT1, is associated with several human cancers, including leukemia. We evaluated WT1 as an immunotherapeutic target using our proven DNA fusion vaccine design, p.DOM-peptide, encoding a minimal tumor-derived major histocompatibility complex (MHC) class I–binding epitope downstream of a foreign sequence of tetanus toxin. Three p.DOM-peptide vaccines, each encoding a different WT1-derived, HLA-A2–restricted epitope, induced cytotoxic T lymphocytes (CTLs) in humanized transgenic mice expressing chimeric HLA-A2, without affecting hematopoietic stem cells. Mouse CTLs 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 epitope were lytic in vitro. Focusing 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]

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