Premium
RD114‐pseudotyped retroviral vectors kill cancer cells by syncytium formation and enhance the cytotoxic effect of the TK/GCV gene therapy strategy
Author(s) -
Germain E.,
Roullin V.G.,
Qiao J.,
de Campos Lima P. O.,
Caruso M.
Publication year - 2005
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.691
Subject(s) - syncytium , cytotoxic t cell , genetic enhancement , viral vector , gene , virology , cancer , cancer research , biology , suicide gene , virus , genetics , in vitro , recombinant dna
Background Wild‐type RD114 virus is capable of generating syncytia during its replication, and it is believed that cell‐free viruses direct the fusion of neighboring cells. The RD114 envelope (Env) that mediates this fusion event is now widely used to pseudotype retroviral and lentiviral vectors in gene therapy. Indeed, vectors pseudotyped with RD114 Env are very efficient to transfer genes into human hematopoietic cells, and they are resistant to human complement inactivation. In this study, we have tested the potential of RD114‐pseudotyped vectors produced from the FLYRD18 packaging cell line to induce syncytia. Methods RD114‐pseudotyped vectors produced from the FLYRD18 packaging cells were added on tumor cell lines, and the formation of syncytia was assessed by microscopy after cell fixation and methylene blue staining. The kinetics of syncytium formation was analyzed by time‐lapse microscopy. Finally, the cytotoxic effect of RD114‐pseudotyped vectors was measured by the MTT assay on tumor cells, and in combination with the TK/GCV strategy. Results We have found that these vectors were able to mediate cell‐to‐cell fusion of human tumor cell lines. A few hours after addition of the vector, cells started to aggregate to form syncytia that eventually evolved toward cell death 48 h postinfection. RD114‐pseudotyped vectors were very efficient at killing human cancer cells, and they were also able to enhance dramatically the cytotoxic effect of the TK/GCV strategy. Conclusions These findings indicate that RD114‐pseudotyped vectors used alone, or in combination with a suicide gene therapy approach, have great potential for the treatment of cancer. Copyright © 2004 John Wiley & Sons, Ltd.