title: High-dose RHAMM-R3 peptide vaccination for patients with acute myeloid leukemia, myelodysplastic syndrome and multiple myeloma.
abstract: BACKGROUND
  Recently, we demonstrated immunological and clinical responses to a RHAMM-R3 peptide vaccine in patients with acute myeloid leukemia, myelodysplastic syndrome and multiple myeloma. To improve the outcome of the vaccine, a second cohort was vaccinated with a higher dose of 1,000 microg peptide.
  
  
  METHODS
  Nine patients received four vaccinations subcutaneously at a biweekly interval. Immunomonitoring of cytotoxic CD8(+) as well as regulatory CD4(+) T cells was performed by flow cytometry as well as by enzyme-linked immunospot (ELISpot) assays. Parameters of clinical response were assessed.
  
  
  RESULTS
  In 4 of 9 patients (44%) we detected positive immunological responses. These patients showed an increase of CD8(+)RHAMM-R3_tetramer(+)/CD45RA(+)/CCR7(-)/CD27(-)/CD28(-) effector T cells and an increase of R3-specific CD8+ T cells. Two of these patients showed a significant decrease of regulatory T cells (Tregs). In one patient without response Tregs frequency increased from 5 to 16%. Three patients showed clinical effects: one patient with myelodysplastic syndrome RAEB-1 showed a reduction of leukemic blasts in the bone marrow, another myelodysplastic syndrome patient an improvement of peripheral blood counts and one patient with multiple myeloma a reduction of free light chains. Clinical and immunological reactions were lower in this cohort than in the 300 microg cohort.
  
  
  CONCLUSIONS
  High-dose RHAMM-R3 peptide vaccination induced immunological responses and positive clinical effects. Therefore, RHAMM constitutes a promising structure for further targeted immunotherapies in patients with different hematologic malignancies. However, higher doses of peptide did not improve the frequency and intensity of immune responses in this trial.
authors.affiliation: Department of Internal Medicine III, University of Ulm, Albert-Einstein-Allee 23 89081 Ulm, Germany. jochen.greiner@uniklinik-ulm.de
authors.forename: Jochen
authors.initials: J
authors.lastname: Greiner
authors.forename: Anita
authors.initials: A
authors.lastname: Schmitt
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Giannopoulos
authors.forename: Markus T
authors.initials: MT
authors.lastname: Rojewski
authors.forename: Marlies
authors.initials: M
authors.lastname: Götz
authors.forename: Isabel
authors.initials: I
authors.lastname: Funk
authors.forename: Mark
authors.initials: M
authors.lastname: Ringhoffer
authors.forename: Donald
authors.initials: D
authors.lastname: Bunjes
authors.forename: Susanne
authors.initials: S
authors.lastname: Hofmann
authors.forename: Gerd
authors.initials: G
authors.lastname: Ritter
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.forename: Michael
authors.initials: M
authors.lastname: Schmitt
mesh_terms: D000368:Aged; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins / Q000008:administration & dosage* / Q000276:immunology; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000008:administration & dosage* / Q000276:immunology; D007109:Immunity / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D010446:Peptide Fragments; C098946:hyaluronan-mediated motility receptor