Background: The ability to kill lymphoid cells with a non-toxic prodrug/gene/
toxin system would be of value in the treatment of lymphoid malignancies and in the regulation
of T cells used in adoptive immunotherapy.
Objective: In this in vitro study we examined the ability of a novel prodrug/gene/toxin
system to produce cytotoxicity in lymphoid cells. The system uses a non-toxic prodrug
ethanol, human alcohol dehydrogenase and exerts the toxic action via the prolonged production
of acetaldehyde produced within targeted cells.
Methods: Raji B cells were transduced with an alcohol dehydrogenase containing lentivirus
and then exposed to differing durations of daily ethanol exposure. Cell numbers and
viability were assessed by trypan blue exclusion.
Results: Individually, ethanol and the ADH gene were non-toxic to Raji B cells. Exposure
of ADH transduced cells to ethanol produced prompt growth inhibition and later cell killing
that could be negated by the presence of 4-MP the alcohol dehydrogenase inhibitor. At
96 hours exposure to ethanol the number of ADH transduced cells had declined by up to
66% and their total number comprised only 2% of the proliferating untreated control cells.
Conclusion: The ethanol ADH acetaldehyde system offers a simple, safe, non-toxic approach
to cancer therapy prodrug toxin technology. It may also offer a safe and non-toxic
system to control the number and action of T cells used in adoptive immunotherapy.