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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1357-1365. Prepublished online as a Blood First Edition Paper on October 31, 2007; DOI 10.1182/blood-2007-07-099366. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-07-099366v1 111/3/1357    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 Schmitt, M. Articles by Greiner, J. PubMed PubMed Citation Articles by Schmitt, M. Articles by Greiner, J. Related Collections Clinical Trials and Observations Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses Michael Schmitt1, Anita Schmitt1, Markus T. Rojewski2, Jinfei Chen1, Krzysztof Giannopoulos3, Fei Fei1, Yingzhe Yu1, Marlies Götz1, Marta Heyduk1, Gerd Ritter4, Daniel E. Speiser5, Sacha Gnjatic4, Philippe Guillaume6, Mark Ringhoffer1, Richard F. Schlenk1, Peter Liebisch1, Donald Bunjes1, Hiroshi Shiku7, Hartmut Dohner1, and Jochen Greiner1 1 Department of Internal Medicine III, University of Ulm, Ulm, Germany; 2 Institute for Transfusion Medicine, University of Ulm and Institute for Clinical Transfusion Medicine and Immunogenetics Ulm Gemeinnützige gGmbH, Ulm, Germany; 3 Lublin Medical University, Department of Clinical Immunology, Lublin, Poland; 4 Ludwig Institute for Cancer Research (LICR) New York Branch, Memorial Sloan-Kettering Cancer Center, New York, NY; 5 Division of Clinical Onco-Immunology, LICR, Hôpital Orthopédique, Lausanne, Switzerland; 6 LICR, Lausanne Branch, University of Lausanne, Epalinges, Switzerland; and 7 Mie University Medical School, Tsu, Japan The receptor for hyaluronic acid–mediated motility (RHAMM) is an antigen eliciting both humoral and cellular immune responses in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma (MM). We initiated a phase 1 clinical trial vaccinating 10 patients with R3 (ILSLELMKL), a highly immunogenic CD8+ T-cell epitope peptide derived from RHAMM. In 7 of 10 patients, we detected an increase of CD8+/HLA-A2/RHAMM R3 tetramer+/CD45RA+/CCR7–/CD27–/CD28– effector T cells in accordance with an increase of R3-specific CD8+ T cells in enzyme linked immunospot (ELISpot) assays. In chromium release assays, a specific lysis of RHAMM-positive leukemic blasts was shown. Three of 6 patients with myeloid disorders (1/3 AML, 2/3 MDS) achieved clinical responses: one patient with AML and one with MDS showed a significant reduction of blasts in the bone marrow after the last vaccination. One patient with MDS no longer needed erythrocyte transfusions after 4 vaccinations. Two of 4 patients with MM showed a reduction of free light chain serum levels. Taken together, RHAMM-R3 peptide vaccination induced both immunologic and clinical responses, and therefore RHAMM constitutes a promising target for further immunotherapeutic approaches. This study is registered at http://ISRCTN.org as ISRCTN32763606 [controlled-trials.com] and is registered with EudraCT as 2005-001706-37. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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