RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses.

Details

Serval ID
serval:BIB_7F167123FF4C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses.
Journal
Blood
Author(s)
Schmitt M., Schmitt A., Rojewski M.T., Chen J., Giannopoulos K., Fei F., Yu Y., Götz M., Heyduk M., Ritter G., Speiser D.E., Gnjatic S., Guillaume P., Ringhoffer M., Schlenk R.F., Liebisch P., Bunjes D., Shiku H., Dohner H., Greiner J.
ISSN
0006-4971 (Print)
ISSN-L
0006-4971
Publication state
Published
Issued date
2008
Volume
111
Number
3
Pages
1357-1365
Language
english
Notes
Publication types: Clinical Trial, Phase I ; Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
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.
Keywords
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
Pubmed
Web of science
Open Access
Yes
Create date
17/01/2012 16:08
Last modification date
20/08/2019 15:39
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