Retroviral transfer of human CD20 as a suicide gene for adoptive T-cell therapy

被引:110
作者
Griffioen, Marieke [1 ]
van Egmond, Esther H. M. [1 ]
Kester, Michel G. D. [1 ]
Willemze, Roel [1 ]
Falkenburg, J. H. Frederik [1 ]
Heemskerk, Mirjam H. M. [1 ]
机构
[1] Leiden Univ, Lab Expt Hematol, Med Ctr, Dept Hematol, NL-2333 ZA Leiden, Netherlands
来源
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL | 2009年 / 94卷 / 09期
关键词
gene therapy; suicide gene; donor lymphocyte infusions; T-cell receptor; MINOR HISTOCOMPATIBILITY ANTIGEN; CASPASE-9 SAFETY SWITCH; VERSUS-HOST-DISEASE; DONOR LYMPHOCYTES; AUTOIMMUNE-DISEASE; LEUKEMIA; TRANSPLANTATION; ANTIBODIES; RITUXIMAB; RESPONSES;
D O I
10.3324/haematol.2008.001677
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
The aim of adoptive T-cell therapy of cancer is to selectively confer immunity against tumor cells. Autoimmune side effects, however, remain a risk, emphasizing the relevance of a suicide mechanism allowing in vivo elimination of infused T cells. We investigated the use of human CD20 as suicide gene in T-lymphocytes. Potential effects of forced CD20 expression on T-cell function were investigated by comparing CD20- and mock-transduced cytomegalovirus (CMV) specific T cells for cytolysis, cytokine release and proliferation. The use of CD20 as suicide gene was investigated in CMV specific T cells and in T cells genetically modified with an antigen specific T-cell receptor. No effect of CD20 on T-cell function was observed. CD20-transduced T cells with and without co-transferred T-cell receptor were efficiently eliminated by complement dependent cytotoxicity induced by therapeutic anti-CD20 antibody rituximab. The data support the broad value of CD20 as safety switch in adoptive T-cell therapy.
引用
收藏
页码:1316 / 1320
页数:5
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