1. Retroviral transfer of human CD20 as a suicide gene for adoptive T-cell therapy.
- Author
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Griffioen M, van Egmond EH, Kester MG, Willemze R, Falkenburg JH, and Heemskerk MH
- Subjects
- Antibodies, Monoclonal, Murine-Derived, Antigens, CD20 immunology, Cell Line, Humans, Neoplasms immunology, Neoplasms metabolism, Rituximab, T-Lymphocytes immunology, T-Lymphocytes metabolism, Antibodies, Monoclonal pharmacology, Antigens, CD20 biosynthesis, Antineoplastic Agents pharmacology, Genes, Transgenic, Suicide, Immunotherapy, Adoptive, Neoplasms therapy, Retroviridae, T-Lymphocytes transplantation, Transduction, Genetic
- 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.
- Published
- 2009
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