| Autor: |
Mirjam H.M. Heemskerk, J.H. Frederik Falkenburg, Peter A. van Veelen, Marieke Griffioen, Inge Jedema, Pieter S. Hiemstra, Cees van Kooten, Gert-Jan Lugthart, Arnoud H. de Ru, Michel D.G. Kester, Renate de Boer, Renate S. Hagedoorn, Marleen M. van Loenen, Dirk M. van der Steen, Avital L. Amir |
| Rok vydání: |
2023 |
| DOI: |
10.1158/1078-0432.c.6519483.v1 |
| Popis: |
Purpose: In human leukocyte antigen (HLA)–matched stem cell transplantation (SCT), it has been shown that beneficial immune response mediating graft-versus-tumor (GVT) responses can be separated from graft-versus-host disease (GVHD) immune responses. In this study, we investigated whether it would be possible to dissect the beneficial immune response of allo-HLA–reactive T cells with potent antitumor reactivity from GVHD-inducing T cells present in the detrimental immune response after HLA-mismatched SCT.Experimental Design: The presence of specific tumor-reactive T cells in the allo-HLA repertoire was analyzed at the time of severe GVHD after HLA-mismatched SCT, using tetramers composed of different tumor-associated antigens (TAA).Results: High-avidity allo-HLA-restricted T cells specific for the TAA preferentially expressed antigen on melanomas (PRAME) were identified that exerted highly single-peptide–specific reactivity. The T cells recognized multiple different tumor cell lines and leukemic cells, whereas no reactivity against a large panel of nonmalignant cells was observed. These T cells, however, also exerted low reactivity against mature dendritic cells (DC) and kidney epithelial cells, which was shown to be because of low PRAME expression.Conclusions: On the basis of potential beneficial specificity and high reactivity, the T-cell receptors of these PRAME-specific T cells may be effective tools for adoptive T-cell therapy. Clinical studies have to determine the significance of the reactivity observed against mature DCs and kidney epithelial cells. Clin Cancer Res; 17(17); 5615–25. ©2011 AACR. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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