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Retroviral transfer of human CD20 as a suicide gene for adoptive T-cell therapy.
- Source :
-
Haematologica [Haematologica] 2009 Sep; Vol. 94 (9), pp. 1316-20. - Publication Year :
- 2009
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1592-8721
- Volume :
- 94
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Haematologica
- Publication Type :
- Academic Journal
- Accession number :
- 19734426
- Full Text :
- https://doi.org/10.3324/haematol.2008.001677