Despite other reports that PC-3 cells did not exhibit strong bystander effects with the HSV-tk/GCV system [ 26 , 27 ], we were able to observe fairly significant bystander cell killing both in vitro and in vivo with our TMPK-F105Y/AZT suicide gene therapy.
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The engineered thymidylate kinase (TMPK)/AZT enzyme-prodrug axis offers efficient bystander cell killing for suicide gene therapy of cancer.
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The bystander killing effect in co-cultures with a 1:4 ratio of eGFP-expressing cells (20%) to TMPK-F105Y-expressing cells (80%) was highly significant leading to an overall 80% decrease in cell survival in the co-cultures following 5 days of AZT treatment ( Figure 2D ), suggesting that a potent bystander killing effect could be observed.