Abstract 5354: The guilty bystander model for electrochemotherapy of cancer: Verification in vitro

• Published in: Cancer research (Chicago, Ill.) Ill.), 2015-08, Vol.75 (15_Supplement), p.5354-5354
• Main Authors: Lambert, W Clark, Tsongalis, Gregory J., Gagna, Claude E., Lambert, Muriel W.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2015-5354

Electroporation (EPR) is the induction of pores in cellular membranes in cells by application of a short application of a high voltage, low amperage electric current. If the cells are immersed in a solution containing a large molecule which is normally impervious to this membrane, it may be introduced into the cells in this manner. Electrochemotherapy (ECT) is a clinical procedure in which a drug, such as bleomicin or cisplatin, is introduced into the blood of or intratumorally into an animal or human subject by intravenous injection followed by application of a short high dose, low amperage electric current into a neoplasm after a delay enabling the drug to reach the neoplasm through the bloodstream or by other means. ECT is normally used for palliative care in human subjects, however there are now a number of reports, numbering well over 10, of unexpected complete clearance of neoplasms following ECT. Many of these reports have come from university centers in Europe and elsewhere. Although ECT is not yet approved in the USA, we believe that these reports can no longer be ignored. We and others have used EPR in culture to introduce large molecules into cells for experimental purposes for decades. Even under the controlled experimental conditions we have employed, however, the proportion of cells into which these molecules have been introduced has been well below 100 per cent. To account for the clearance of some tumors by ECT, in which the proportion of cells in which drug is introduced would be expected to be lower than for EPR, we have proposed a “Guilty Bystander Model”, in which cells adjacent to neoplastic cells into which drug has been introduced are also cleared. To test this model in vitro, we optimized conditions for EPR but were unable to produce more than 88 per cent introduction of labeled large molecules into lymphoblastoid cells (GM 1989A, derived from a healthy 33 year old Caucasian male, and GM 3999, derived from a healthy 8 year old Caucasian female), even under conditions which reduced cell viability from 99 per cent to 79 per cent. Increasing voltage produced a marked loss of viability. We conclude that EPR does not produce 100 per cent introduction of large molecules into human cells, even under optimized conditions in vitro, and that there must remain neoplastic cells in tumors treated by ECT that are eliminated by means other than introduction of the drug. Citation Format: W Clark Lambert, Gregory J. Tsongalis, Claude E. Gagna, Murie