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Blood, 15 June 2006, Vol. 107, No. 12, pp. 4954-4960.
Prepublished online as a Blood First Edition Paper on February 23, 2006; DOI 10.1182/blood-2005-09-3883.
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Submitted September 28, 2005
Accepted February 11, 2006
Identification of the angiogenic endothelial cell growth factor-1/thymidine phosphorylase as a potential target for immunotherapy of cancer
Elisabeth H Slager*, M W Honders, Edith D van der Meijden, Simone A van Luxemburg-Heijs, Freke M Kloosterboer, Michel G Kester, Inge Jedema, Erik Marijt, M R Schaafsma, Roel Willemze, and Frederik Falkenburg
Laboratory of Experimental Hematology, Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
Department of Hematology, Medisch Spectrum Twente, Enschede, The Netherlands
* Corresponding author; email: e.h.slager{at}lumc.nl.
Characterization of the antigens recognized by tumor-reactive T cells isolated from patients successfully treated with allogeneic HLA-matched hematopoietic stem cell transplantation (SCT) can lead to the identification of clinically relevant target molecules. We isolated tumor-reactive cytotoxic CD8+ T cell (CTL) clones from a patient successfully treated with donor lymphocyte infusion for relapsed multiple myeloma after allogeneic HLA-matched SCT. Using cDNA expression cloning, the target molecule of a HLA-B7-restricted CTL clone was identified. The CTL clone recognized a minor histocompatibility antigen produced by a single nucleotide polymorphism (SNP) in the angiogenic endothelial cell growth factor-1 (ECGF-1) gene also known as thymidine phosphorylase. The SNP leads to an Arg-to-His substitution in an alternatively translated peptide that is recognized by the CTL. The ECGF-1 gene is predominantly expressed in hematopoietic cells, although low expression can also be detected in other tissues. The patient from whom this CTL clone was isolated had mild graft-versus-host disease despite high numbers of circulating ECGF-1-specific T cells as detected by tetramer staining. Since solid tumors expressing ECGF-1 could also be lysed by the CTL, ECGF-1 is an interesting target for immunotherapy of both hematological and solid tumors.

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