RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses Journal Article
| Authors: | 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.; Döhner, H.; Greiner, J. |
| Article Title: | RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses |
| 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. © 2008 by The American Society of Hematology. |
| Keywords: | clinical article; controlled study; treatment response; unclassified drug; acute granulocytic leukemia; leukemia, myeloid, acute; clinical trial; cd8+ t lymphocyte; cd8-positive t-lymphocytes; interleukin 2; multiple cycle treatment; multiple myeloma; etoposide; interleukin 10; dexamethasone; melphalan; enzyme linked immunosorbent assay; ifosfamide; fever; myelodysplastic syndrome; immune response; immunotherapy; peptide fragments; vaccination; epitope; epirubicin; cytotoxicity, immunologic; bone marrow cell; phase 1 clinical trial; idarubicin; peptide vaccine; chemokine receptor ccr7; immunoglobulin light chain; injection site erythema; cd28 antigen; myelodysplastic syndromes; cd27 antigen; cd45ra antigen; hla a2 antigen; blast cell; vitiligo; antigens, cd44; injection site induration; rhamm r3 peptide; autoimmune thyroiditis; chromium 51 release; rheumatic disease; extracellular matrix proteins |
| Journal Title: | Blood |
| Volume: | 111 |
| Issue: | 3 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2008-02-01 |
| Start Page: | 1357 |
| End Page: | 1365 |
| Language: | English |
| DOI: | 10.1182/blood-2007-07-099366 |
| PUBMED: | 17978170 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 51" - "Export Date: 17 November 2011" - "CODEN: BLOOA" - "Source: Scopus" |
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