title: RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses.
abstract: 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 and is registered with EudraCT as 2005-001706-37.
authors.affiliation: Department of Internal Medicine III, University of Ulm, Ulm, Germany. michael.schmitt@uniklinik-ulm.de
authors.forename: Michael
authors.initials: M
authors.lastname: Schmitt
authors.forename: Anita
authors.initials: A
authors.lastname: Schmitt
authors.forename: Markus T
authors.initials: MT
authors.lastname: Rojewski
authors.forename: Jinfei
authors.initials: J
authors.lastname: Chen
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Giannopoulos
authors.forename: Fei
authors.initials: F
authors.lastname: Fei
authors.forename: Yingzhe
authors.initials: Y
authors.lastname: Yu
authors.forename: Marlies
authors.initials: M
authors.lastname: Götz
authors.forename: Marta
authors.initials: M
authors.lastname: Heyduk
authors.forename: Gerd
authors.initials: G
authors.lastname: Ritter
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Speiser
authors.forename: Sacha
authors.initials: S
authors.lastname: Gnjatic
authors.forename: Philippe
authors.initials: P
authors.lastname: Guillaume
authors.forename: Mark
authors.initials: M
authors.lastname: Ringhoffer
authors.forename: Richard F
authors.initials: RF
authors.lastname: Schlenk
authors.forename: Peter
authors.initials: P
authors.lastname: Liebisch
authors.forename: Donald
authors.initials: D
authors.lastname: Bunjes
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiku
authors.forename: Hartmut
authors.initials: H
authors.lastname: Dohner
authors.forename: Jochen
authors.initials: J
authors.lastname: Greiner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D016326:Extracellular Matrix Proteins / Q000009:adverse effects / Q000276:immunology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000009:adverse effects / Q000276:immunology*; D007167:Immunotherapy; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000628:therapy; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology* / Q000628:therapy; D009190:Myelodysplastic Syndromes / Q000276:immunology* / Q000628:therapy; D010446:Peptide Fragments / Q000009:adverse effects / Q000276:immunology*; D014611:Vaccination / Q000009:adverse effects
chemical_list: D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D010446:Peptide Fragments; C098946:hyaluronan-mediated motility receptor