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Blood, 19 February 2009, Vol. 113, No. 8, pp. 1651-1660. Prepublished online as a Blood First Edition Paper on December 12, 2008; DOI 10.1182/blood-2008-07-168666. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2008-07-168666v1 113/8/1651    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 Citing Articles via Google Scholar Google Scholar Articles by Fontana, R. Articles by Russo, V. Search for Related Content PubMed PubMed Citation Articles by Fontana, R. Articles by Russo, V. Related Collections Immunobiology Clinical Trials and Observations Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Peripheral blood lymphocytes genetically modified to express the self/tumor antigen MAGE-A3 induce antitumor immune responses in cancer patients Raffaella Fontana1, Marco Bregni2, Arcadi Cipponi1, Laura Raccosta1, Cristina Rainelli1, Daniela Maggioni1, Francesca Lunghi3, Fabio Ciceri3, Sylvain Mukenge4, Claudio Doglioni5, Didier Colau6,7, Pierre G. Coulie6, Claudio Bordignon1,3,8,9, Catia Traversari9,*, and Vincenzo Russo1,* 1 Cancer Gene Therapy Unit, Cancer Immunotherapy and Gene Therapy Program, Department of Oncology, 2 Strategic Program of Oncology, 3 Bone Marrow Transplantation Unit, 4 Department of Surgery, and 5 Department of Pathology, Scientific Institute San Raffaele, Milan, Italy; 6 de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; 7 Ludwig Institute for Cancer Research, Brussels, Belgium; 8 Università Vita-Salute San Raffaele, Milan, Italy; and 9 MolMed SpA, Milan, Italy Dendritic cell (DC) targeting in vivo has recently been shown to confer strong and protective cytotoxic T lymphocyte (CTL)–based immunity in tumor murine models. Our group has recently demonstrated in preclinical models that the infusion of genetically modified lymphocytes (GMLs) expressing the self/tumor antigen TRP-2 is able to elicit functional TRP-2–specific effectors with antitumor activity by targeting DCs in vivo. Here we have analyzed vaccine- and tumor-specific immune responses of 10 melanoma patients treated with autologous GMLs expressing the cancer germline gene MAGE-A3. Three of 10 patients treated with MAGE-A3–GML showed an increase of circulating anti–MAGE-A3 T cells, and developed skin delayed-type hypersensitivity to MAGE-A3. Interestingly, in 2 of these patients, with progressive and measurable tumors at study entry, anti–MAGE-A3 T cells were detected not only in the blood but also within tumors resected after vaccination. These results demonstrate that the infusion of MAGE-A3–GML elicits antitumor T cells, which are capable of trafficking to inflamed tissues and of infiltrating tumors. Clinical studies on a larger group of patients are needed to evaluate the clinical efficacy of such a strategy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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