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

• Published in: Haematologica (Roma) 2009-09, Vol.94 (9), p.1316-1320
• Main Authors: Griffioen, Marieke, van Egmond, Esther H.M, Kester, Michel G.D, Willemze, Roel, Falkenburg, J.H. Frederik, Heemskerk, Mirjam H.M
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal, Murine-Derived; Antigens, CD20 - biosynthesis; Antigens, CD20 - immunology; Antineoplastic Agents - pharmacology; Biological and medical sciences; Brief Reports; Cell Line; Genes, Transgenic, Suicide; Hematologic and hematopoietic diseases; Humans; Immunotherapy, Adoptive; Medical sciences; Neoplasms - immunology; Neoplasms - metabolism; Neoplasms - therapy; Retroviridae; Rituximab; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - transplantation; Transduction, Genetic
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2008.001677

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.