Title:Growth Retardation of Poorly Transfectable Tumor by Multiple Injections of Plasmids Encoding PE40 Based Targeted Toxin Complexed with Polyethylenimine
Volume: 20
Issue: 4
Author(s): Yuriy Khodarovich*, Darya Rakhmaninova, German Kagarlitskiy, Anastasia Baryshnikova and Sergey Deyev
Affiliation:
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow,Russian Federation
Keywords:
Gene therapy, pseudomonas exotoxin A, PE40, targeted therapy, transfection, polyethylenimine.
Abstract:
Background: One of the approaches to cancer gene therapy relies on tumor transfection
with DNA encoding toxins under the control of tumor-specific promoters.
Methods: Here, we used DNA plasmids encoding very potent anti-ERBB2 targeted toxin, driven by
the human telomerase promoter or by the ubiquitous CAG promoter (pTERT-ETA and pCAG-ETA)
and linear polyethylenimine to target cancer cells.
Results: We showed that the selectivity of cancer cell killing by the pTERT-ETA plasmid is highly
dependent upon the method of preparation of DNA-polyethylenimine complexes. After adjustment of
complex preparation protocol, cell lines with high activity of telomerase promoter can be selectively
killed by transfection with the pTERT-ETA plasmid. We also showed that cells transfected with
pTERT-ETA and pCAG-ETA plasmids do not exert any detectable bystander effect in vitro.
Conclusion: Despite this, three intratumoral injections of a plasmid-polyethylenimine complex resulted
in substantial growth retardation of a poorly transfectable D2F2/E2 tumor in mice. There were no
significant differences in anti-tumor properties between DNA constructs with telomerase or CAG
promoters in vivo.
