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Growth Retardation of Poorly Transfectable Tumor by Multiple Injections of Plasmids Encoding PE40 Based Targeted Toxin Complexed with Polyethylenimine

Author(s):

Yuriy Khodarovich*, Darya Rakhmaninova, German Kagarlitskiy, Anastasia Baryshnikova and Sergey Deyev   Pages 1 - 8 ( 8 )

Abstract:


Background: One of the approaches to cancer gene therapy relies on tumor transfection with DNA encoding tox-ins under 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 pTERT-ETA plasmid is highly dependent upon method of preparation of DNA- polyethylenimine complexes. After adjustment of complex preparation protocol cell lines with high ac-tivity of telomerase promoter can be selectively killed by transfection with pTERT-ETA plasmid. We also show 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 a substantial growth retardation of poorly transfectable D2F2/E2 tumor in mice. There were no significant differences in anti-tumor prop-erties between DNA constructs with telomerase or CAG promoters in vivo.

Keywords:

gene therapy, Pseudomonas exotoxin A, PE40, targeted therapy, transfection, polyethylenimine

Affiliation:

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow,, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow,, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow,, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow,, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow



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