Article: article from journal or magazin.
RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses.
Publication types: Clinical Trial, Phase I ; Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
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.
Adult, Aged, Aged, 80 and over, Antigens, CD44/adverse effects, Antigens, CD44/immunology, CD8-Positive T-Lymphocytes/immunology, Cytotoxicity, Immunologic/immunology, Extracellular Matrix Proteins/adverse effects, Extracellular Matrix Proteins/immunology, Humans, Immunotherapy, Leukemia, Myeloid, Acute/immunology, Leukemia, Myeloid, Acute/therapy, Middle Aged, Multiple Myeloma/immunology, Multiple Myeloma/therapy, Myelodysplastic Syndromes/immunology, Myelodysplastic Syndromes/therapy, Peptide Fragments/adverse effects, Peptide Fragments/immunology, Vaccination/adverse effects
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