Identification of the angiogenic endothelial-cell growth factor-1/thymidine phosphorylase as a potential target for immunotherapy of cancer
| Autor: | M. Willy Honders, Inge Jedema, Elisabeth H. Slager, Michel G.D. Kester, Roel Willemze, M. Ron Schaafsma, J.H. Frederik Falkenburg, Freke M. Kloosterboer, Simone A.P. van Luxemburg-Heijs, W. A. Erik Marijt, Edith D. van der Meijden |
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| Rok vydání: | 2006 |
| Předmět: |
Immunology
Molecular Sequence Data Clone (cell biology) Graft vs Host Disease Biology CD8-Positive T-Lymphocytes Biochemistry Polymorphism Single Nucleotide Donor lymphocyte infusion Antigen Minor histocompatibility antigen Cytotoxic T cell Humans Transplantation Homologous Thymidine phosphorylase Thymidine Phosphorylase Base Sequence Hematopoietic Stem Cell Transplantation Cell Biology Hematology Hematopoietic Stem Cells Gene Expression Regulation Neoplastic CTL Amino Acid Substitution Lymphocyte Transfusion Cancer research Immunotherapy Multiple Myeloma CD8 |
| Zdroj: | Blood. 107(12) |
| ISSN: | 0006-4971 |
| Popis: | 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 an 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 (ECGF1) 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 ECGF1 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. Because solid tumors expressing ECGF-1 could also be lysed by the CTL, ECGF-1 is an interesting target for immunotherapy of both hematologic and solid tumors. |
| Databáze: | OpenAIRE |
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