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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 (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 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 Schmitt, M. Articles by Greiner, J. Search for Related Content PubMed PubMed Citation Articles by Schmitt, M. Articles by Greiner, J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 9, 2007 Accepted October 14, 2007 RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome and multiple myeloma elicits immunological and clinical responses Michael Schmitt*, Anita Schmitt, Markus T Rojewski, Jinfei Chen, Krzysztof Giannopoulos, Fei Fei, Yingzhe Yu, Marlies Gotz, Marta Heyduk, Gerd Ritter, Daniel E Speiser, Sacha Gnjatic, Philippe Guillaume, Mark Ringhoffer, Richard F Schlenk, Peter Liebisch, Donald Bunjes, Hiroshi Shiku, Hartmut Dohner, and Jochen Greiner Department of Internal Medicine III, University of Ulm, Ulm, Germany Institute for Transfusion Medicine, University of Ulm, & Institute for Clincal Transfusion Medicine & Immunogenetics Ulm gemeinnutzige GmbH, Ulm, Germany Dept. of Clinical Immunology, Lublin Medical University, Lublin, Poland Ludwig Institute for Cancer Research (LICR) New York Branch, Memorial Sloan-Kettering Cancer Center, New York, NY, United States Division of Clinical Onco-Immunology, LICR, Hopital Orthopedique, Lausanne, Switzerland LICR, Lausanne Branch, University of Lausanne, Epalinges, Switzerland Mie University Medical School, Tsu, Japan * Corresponding author; email: michael.schmitt{at}uniklinik-ulm.de. 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 I clinical trial vaccinating ten patients four times at a biweekly interval with R3 (ILSLELMKL), a highly immunogenic CD8+ T cell epitope peptide derived from RHAMM. In 7/10 patients, we detected an increase of CD8+/HLA-A2/RHAMM R3 tetramer+/CD45RA+/CCR7-/CD27-/CD28- effector T cells in flow cytometry 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. 3/6 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 three weeks after the last vaccination. One patient with MDS did not need any longer erythrocyte transfusions after four vaccinations. Two of four patients with MM showed a reduction of free light chain serum levels. Taken together, RHAMM-R3 peptide vaccination induced both immunological and clinical responses, and therefore RHAMM constitutes a promising target for further immunotherapeutical approaches. This study is registered at http://ISRCTN.org as ISRCTN32763606 and is registered with EudraCT as 2005-001706-37. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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