Improving the safety of cell therapy products by suicide gene transfer

The gene transfer of a suicide gene, such as the herpes simplex virus thymidine kinase (HSV-tk) was initially intended to target and destroy tumor cells, taking advantage of its bystander effect to kill gene-modified and non modified tumor cells. The suicide gene transfer was used later as a safety system in order to control the alloreactivity of donor lymphocytes infused as a cell therapy product after hematopoietic cell transplantation. With increasing safety concerns related to the use of ex vivo expanded stem cells or induced progenitor cells, the prior gene transfer of a suicide gene in cell therapy products becomes an emerging approach to secure the product in case of in vivo oncogenic transformation.

This Frontiers in Research Topic is aimed at presenting the suicide gene approach as a safety system for cell therapy products, with especially:
(1) the different suicide gene systems available to date, based, as an example, on the use of prodrug-converting enzymes or the expression of targets of monoclonal antibodies or controllable inducers of apoptosis, with their respective advantages
(2) the methods and vectors used to introduce the suicide gene in target cells
(3) the limits of the use of suicide genes, such as mechanisms of resistance to the prodrugs, immune responses toward gene-modified cells…
(4) the monitoring of suicide gene-modified cells and the possibility to image them in vivo

This Topic will not be restricted to T cells, for which a large set of data have been published, and will also address other type of cell therapy products.