|
|
Blood, 1 August 2005, Vol. 106, No. 3, pp. 938-945.
Prepublished online as a Blood First Edition Paper on April 12, 2005; DOI 10.1182/blood-2004-12-4787.
 Previous Article | Next Article 
Submitted December 16, 2004
Accepted March 14, 2005
Identification and characterization of epitopes of the receptor for hyaluronic acid mediated motility (RHAMM/CD168) recognized by CD8 positive T cells of HLA-A2 positive patients with acute myeloid leukemia
Jochen Greiner, Li Li, Mark Ringhoffer, Thomas F Barth, Krzysztof Giannopoulos, Phillipe Guillaume, Gerd Ritter, Markus Wiesneth, Hartmut Dohner, and Michael Schmitt*
3rd Dept. of Internal Medicine, University of Ulm, Ulm, Germany
Institute for Pathology, University of Ulm, Ulm, Germany
Ludwig Institute for Cancer Research (LICR), Lausanne Branch, University of Lausanne, Epalinges, Switzerland
LICR New York Branch, Memorial Sloan-Kettering Cancer Center, New York, USA
Institute for Immunogenetics and Clinical Transfusion Medicine, German Red Cross, Ulm, Germany
* Corresponding author; email: michael.schmitt{at}medizin.uni-ulm.de.
The receptor for hyaluronic acid mediated motility (RHAMM/CD168) has been described as a leukemia-associated antigen. To define T cell epitopes of RHAMM/CD168 towards specific immunotherapies for acute myeloid leukemia (AML), ten potential HLA-A2 binding RHAMM/CD168-peptides (R1-R10) were synthesized based on computer algorithms and screened by ELISPOT analysis using CD8+ T cells isolated from peripheral blood (PB) of AML patients and healthy donors. We found that CD8+ cells from 7/13 (54%) AML patients presensitized with peptides R3 (ILSLELMKL) or R5 (SLEENIVIL) specifically recognized T2 cells pulsed with R3 (39%) or R5 (15%) peptide. In contrast, only 4/21 (19%) healthy volunteers had CD8+ cells reactive with R3 or R5 pulsed T2 cells after presensitization. The presence of R3 peptide specific effector T cells in the peripheral blood of AML patients could be confirmed by staining as HLA-A2/R3 peptide tetramer+CCR7-CD45RA+cells. In chromium-51 release assays, peptide primed CD8+ T cells from AML patients were able to lyse RHAMM/CD168 peptide pulsed T2 cells, AML blasts and dendritic cells generated thereof (AML-DCs). Transfection of COS-7 cells with RHAMM/CD168 cDNA revealed that peptides R3 and R5 are naturally processed epitopes of RHAMM/CD168 that are presented in a HLA-A2 restricted manner. In summary, RHAMM/CD168 is a promising target for immunotherapies in AML patients and we have therefore initiated a clinical vaccination trial with R3 peptide. As RHAMM/CD168 is also expressed in various other hematological malignancies and solid tumors, therefore vaccines targeting this antigen may have even wider application.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
J. Greiner, L. Bullinger, B.-a. Guinn, H. Dohner, and M. Schmitt
Leukemia-Associated Antigens Are Critical for the Proliferation of Acute Myeloid Leukemia Cells
Clin. Cancer Res.,
November 15, 2008;
14(22):
7161 - 7166.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Schmitt, A. Schmitt, M. T. Rojewski, J. Chen, K. Giannopoulos, F. Fei, Y. Yu, M. Gotz, M. Heyduk, G. Ritter, et al.
RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses
Blood,
February 1, 2008;
111(3):
1357 - 1365.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Greiner, M. Schmitt, L. Li, K. Giannopoulos, K. Bosch, A. Schmitt, K. Dohner, R. F. Schlenk, J. R. Pollack, H. Dohner, et al.
Expression of tumor-associated antigens in acute myeloid leukemia: implications for specific immunotherapeutic approaches
Blood,
December 15, 2006;
108(13):
4109 - 4117.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
