Retroviral transfer of human CD20 as a suicide gene for adoptive T-cell therapy.
Haematologica
; 94(9): 1316-20, 2009 Sep.
Article
in En
| MEDLINE
| ID: mdl-19734426
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Retroviridae
/
Transduction, Genetic
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T-Lymphocytes
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Immunotherapy, Adoptive
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Antigens, CD20
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Genes, Transgenic, Suicide
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Antibodies, Monoclonal
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Neoplasms
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
Haematologica
Year:
2009
Document type:
Article
Affiliation country: