Retroviral transfer of human CD20 as a suicide gene for adoptive T-cell therapy.
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.
Griffioen
Marieke
M
Department of Hematology, Laboratory of Experimental Hematology, Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands. M.Griffioen@lumc.nl
van Egmond
Esther H M
EH
Kester
Michel G D
MG
Willemze
Roel
R
Falkenburg
J H Frederik
JH
Heemskerk
Mirjam H M
MH
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000096:biosynthesis* / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002460:Cell Line; D041722:Genes, Transgenic, Suicide; D006801:Humans; D016219:Immunotherapy, Adoptive; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D012190:Retroviridae; D000069283:Rituximab; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D014161:Transduction, Genetic
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D000069283:Rituximab