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Blood, 1 November 2005, Vol. 106, No. 9, pp. 3105-3113. Prepublished online as a Blood First Edition Paper on July 19, 2005; DOI 10.1182/blood-2005-04-1487.
Submitted April 13, 2005
Medizinische Klinik I, Saarland University Medical School, Homburg, Germany * Corresponding author; email: michael.pfreundschuh{at}uniklinik-saarland.de.
Due to their frequent expression in a wide spectrum of malignant tumors, but not in normal tissues except testis, cancer testis antigens are promising targets. However, except for HOM-TES-14/SCP1 their expression in malignant lymphomas is rare. SCP1 has been shown to elicit antibody responses in the autologous host, but no T-cell responses against HOM-TES-14/SCP1 have been reported. Using the SYFPEITHI algorithm we selected peptides with a high binding affinity to MHC-II molecules. The pentadecamer epitope p635-649 induced specific CD4+ T-cell responses which were shown to be restricted by HLA-DRB1*1401. The responses could be blocked by preincubation of T cells with anti-CD4 and antigen-presenting cells with anti-HLA-DR, respectively, proving the HLA-DR restricted presentation of p635-649 and a CD4+ T-cell mediated effector response. Responding CD4+ cells did not secrete IL-5 indicating that they belong to the TH1 subtype. The natural processing and presentation of p635-649 was demonstrated by pulsing autologous and allogeneic dendritic cells with a protein fragment covering p635-649. Thus, p635-649 is the first HOM-TES-14/SCP1 derived epitope to fulfill all prerequisites for use as a peptide vaccine in patients with HOM-TES-14/SCP1 expressing tumors, which is the case in two thirds of peripheral T-cell lymphomas.
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