RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses.
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.
Schmitt
Michael
M
Department of Internal Medicine III, University of Ulm, Ulm, Germany. michael.schmitt@uniklinik-ulm.de
Schmitt
Anita
A
Rojewski
Markus T
MT
Chen
Jinfei
J
Giannopoulos
Krzysztof
K
Fei
Fei
F
Yu
Yingzhe
Y
Götz
Marlies
M
Heyduk
Marta
M
Ritter
Gerd
G
Speiser
Daniel E
DE
Gnjatic
Sacha
S
Guillaume
Philippe
P
Ringhoffer
Mark
M
Schlenk
Richard F
RF
Liebisch
Peter
P
Bunjes
Donald
D
Shiku
Hiroshi
H
Dohner
Hartmut
H
Greiner
Jochen
J
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
D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D010446:Peptide Fragments; C098946:hyaluronan-mediated motility receptor