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

• Published in: Blood 2008-02, Vol.111 (3), p.1357-1365
• Main Authors: Schmitt, Michael, Schmitt, Anita, Rojewski, Markus T., Chen, Jinfei, Giannopoulos, Krzysztof, Fei, Fei, Yu, Yingzhe, Götz, Marlies, Heyduk, Marta, Ritter, Gerd, Speiser, Daniel E., Gnjatic, Sacha, Guillaume, Philippe, Ringhoffer, Mark, Schlenk, Richard F., Liebisch, Peter, Bunjes, Donald, Shiku, Hiroshi, Dohner, Hartmut, Greiner, Jochen
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Biological and medical sciences; 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; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Immunotherapy; Leukemia, Myeloid, Acute - immunology; Leukemia, Myeloid, Acute - therapy; Medical sciences; Middle Aged; Multiple Myeloma - immunology; Multiple Myeloma - therapy; Myelodysplastic Syndromes - immunology; Myelodysplastic Syndromes - therapy; Peptide Fragments - adverse effects; Peptide Fragments - immunology; Pharmacology. Drug treatments; Vaccination - adverse effects
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2007-07-099366

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.