Optimization of the HA-1-specific T-cell receptor for gene therapy of hematologic malignancies

被引：30

作者：

van Loenen, Marleen M. ^{[1
]}

de Boer, Renate ^{[1
]}

Hagedoorn, Renate S. ^{[1
]}

van Egmond, Esther H. M. ^{[1
]}

Falkenburg, J. H. Frederik ^{[1
]}

Heemskerk, Mirjam H. M. ^{[1
]}

机构：

[1] Leiden Univ, Med Ctr, Dept Hematol, NL-2300 RC Leiden, Netherlands

来源：

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL | 2011年 / 96卷 / 03期

关键词：

gene transfer; T-cell receptors; adoptive immunotherapy; TCR optimization; MINOR HISTOCOMPATIBILITY ANTIGENS; TCR CHAINS; EXPRESSION; LEUKEMIA;

D O I：

10.3324/haematol.2010.025916

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

To broaden the applicability of adoptive T-cell therapy for the treatment of hematologic malignancies, we aim to start a clinical trial using HA-1-TCR transferred virus-specific T cells. TCRs directed against the minor histocompatibility antigen (MiHA) HA-1 are good candidates for TCR gene transfer to treat hematologic malignancies because of the hematopoiesis-restricted expression and favorable frequency of HA-1. For optimal anti-leukemic reactivity, high cell-surface expression of the introduced TCR is important. Previously, however, we have demonstrated that gene transferred HA-1-TCRs are poorly expressed at the cell-surface. In this study several strategies were explored to improve expression of transferred HA-1-TCRs.

引用

页码：477 / 481

页数：5

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