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Forschungsdatenbank PMU-SQQUID

RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses.
Schmitt, M; Schmitt, A; Rojewski, MT; Chen, J; Giannopoulos, K; Fei, F; Yu, Y; Götz, M; Heyduk, M; Ritter, G; Speiser, DE; Gnjatic, S; Guillaume, P; Ringhoffer, M; Schlenk, RF; Liebisch, P; Bunjes, D; Shiku, H; Dohner, H; Greiner, J;
Blood. 2008; 111(3):1357-1365
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Heyduk Marta

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.


Useful keywords (using NLM MeSH Indexing)

Adult

Aged

Aged, 80 and over

CD8-Positive T-Lymphocytes/immunology

Cytotoxicity, Immunologic/immunology

Extracellular Matrix Proteins/adverse effects

Extracellular Matrix Proteins/immunology*

Humans

Hyaluronan Receptors/adverse effects

Hyaluronan Receptors/immunology*

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