High-dose RHAMM-R3 peptide vaccination for patients with acute myeloid leukemia, myelodysplastic syndrome and multiple myeloma.
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.
Greiner
Jochen
J
Department of Internal Medicine III, University of Ulm, Albert-Einstein-Allee 23 89081 Ulm, Germany. jochen.greiner@uniklinik-ulm.de
Schmitt
Anita
A
Giannopoulos
Krzysztof
K
Rojewski
Markus T
MT
Götz
Marlies
M
Funk
Isabel
I
Ringhoffer
Mark
M
Bunjes
Donald
D
Hofmann
Susanne
S
Ritter
Gerd
G
Döhner
Hartmut
H
Schmitt
Michael
M
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
D019496:Cancer Vaccines; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D010446:Peptide Fragments; C098946:hyaluronan-mediated motility receptor