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

被引：172

作者：

Schmitt, Michael ^{[1
]}

Schmitt, Anita ^{[1
]}

Rojewski, Markus T. ^{[2
]}

Chen, Jinfei ^{[1
]}

Giannopoulos, Krzysztof ^{[3
]}

Fei, Fei ^{[1
]}

Yu, Yingzhe ^{[1
]}

Goetz, Marlies ^{[1
]}

Heyduk, Marta ^{[1
]}

Ritter, Gerd ^{[4
]}

Speiser, Daniel E. ^{[5
]}

Gnjatic, Sacha ^{[4
]}

Guillaume, Philippe ^{[6
]}

Ringhoffer, Mark ^{[1
]}

Schlenk, Richard F. ^{[1
]}

Liebisch, Peter ^{[1
]}

Bunjes, Donald ^{[1
]}

Shiku, Hiroshi ^{[7
]}

Dohner, Hartmut ^{[1
]}

Greiner, Jochen ^{[1
]}

机构：

[1] Univ Ulm, Dept Internal Med 3, D-89081 Ulm, Germany

[2] Univ Ulm, Inst Transfus Med, Inst Clin Transfus Med, Immunogenet Ulm Gemeinnutzige gGmbH, Ulm, Germany

[3] Med Univ Lublin, Dept Clin Immunol, Lublin, Poland

[4] Mem Sloan Kettering Canc Ctr, Ludwig Inst Canc Res, New York Branch, New York, NY USA

[5] Hop Orthoped, LICR, Div Oncol Immunol Clin, Lausanne, Switzerland

[6] Univ Lausanne, LICR, Lausanne Branch, Epalinges, Switzerland

[7] Mie Univ, Sch Med, Tsu, Mie, Japan

来源：

BLOOD | 2008年 / 111卷 / 03期

关键词：

D O I：

10.1182/blood-2007-07-099366

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 Eu-draCT as 2005-001706-37.

引用

页码：1357 / 1365

页数：9

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