Retroviral transfer of human CD20 as a suicide gene for adoptive T-cell therapy |
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Authors: | Marieke Griffioen Esther H.M. van Egmond Michel G.D. Kester Roel Willemze J.H. Frederik Falkenburg Mirjam H.M. Heemskerk |
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Affiliation: | Laboratory of Experimental Hematology, Leiden University Medical Center, Leiden, The Netherlands |
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Abstract: | 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. |
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Keywords: | gene therapy suicide gene donor lymphocyte infusions T-cell receptor |
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