Haematologica, Vol 94, Issue 9, 1316-1320 doi:10.3324/haematol.2008.001677
Copyright © 2009 by Ferrata Storti Foundation
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Cell Therapy and Immunotherapy

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

Marieke Griffioen, Esther H.M. van Egmond, Michel G.D. Kester, Roel Willemze, J.H. Frederik Falkenburg, Mirjam H.M. Heemskerk

Laboratory of Experimental Hematology, Leiden University Medical Center, Leiden, The Netherlands

Correspondence: Marieke Griffioen, Dept. of Hematology, C2-R, Albinusdreef 2 2333 ZA Leiden, The Netherlands. E-mail:M.Griffioen{at}lumc.nl

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.

Key words: gene therapy, suicide gene, donor lymphocyte infusions, T-cell receptor.




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M. H.M. Heemskerk
T-cell receptor gene transfer for the treatment of leukemia and other tumors
Haematologica, January 1, 2010; 95(1): 15 - 19.
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