Abstract
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.
Keywords: G-DEPT, cancer, gene therapy, ethanol, acetaldehyde, T cells.
Graphical Abstract
Current Pharmacogenomics and Personalized Medicine
Title:Enhanced Sensitivity of Lymphoid Cells to Ethanol ADH Acetaldehyde Toxicity; Implications for GDEPT and Adoptive T Cell Therapy
Volume: 16
Author(s): Philip Savage*, Claire Horlock, Bryony Stott and Justin Stebbing
Affiliation:
- Department of Medical Oncology, Imperial Hospitals NHS Trust, London,United Kingdom
Keywords: G-DEPT, cancer, gene therapy, ethanol, acetaldehyde, T cells.
Abstract: 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.
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Cite this article as:
Savage Philip*, Horlock Claire, Stott Bryony and Stebbing Justin, Enhanced Sensitivity of Lymphoid Cells to Ethanol ADH Acetaldehyde Toxicity; Implications for GDEPT and Adoptive T Cell Therapy, Current Pharmacogenomics and Personalized Medicine 2018; 16 (2) . https://dx.doi.org/10.2174/1875692116666180703151538
DOI https://dx.doi.org/10.2174/1875692116666180703151538 |
Print ISSN 1875-6921 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6913 |
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