Growth Retardation of Poorly Transfectable Tumor by Multiple Injections of Plasmids Encoding PE40 Based Targeted...

Area of Science:

• Oncology
• Gene Therapy
• Molecular Biology

Background:

• Cancer gene therapy utilizes tumor transfection with DNA encoding toxins.
• Tumor-specific promoters control the expression of these therapeutic toxins.

Purpose of the Study:

• To evaluate DNA plasmids encoding an anti-ERBB2 toxin driven by telomerase or CAG promoters for cancer cell targeting.
• To assess the efficacy of DNA-polyethylenimine complexes in cancer gene therapy.

Main Methods:

• Utilized DNA plasmids (pTERT-ETA and pCAG-ETA) encoding a potent anti-ERBB2 toxin.
• Employed linear polyethylenimine for targeted delivery of DNA plasmids to cancer cells.
• Investigated the impact of DNA-polyethylenimine complex preparation on transfection selectivity and efficacy.

Main Results:

• Selectivity of cancer cell killing by pTERT-ETA was dependent on DNA-polyethylenimine complex preparation.
• Optimized protocols enabled selective killing of cells with high telomerase promoter activity.
• No significant bystander effect was observed in vitro for pTERT-ETA and pCAG-ETA transfected cells.
• Intratumoral injections of plasmid-polyethylenimine complexes significantly retarded D2F2/E2 tumor growth in mice.

Conclusions:

• Optimized DNA-polyethylenimine complex preparation enhances the selectivity of cancer gene therapy.
• The anti-ERBB2 toxin delivered via plasmids shows in vivo anti-tumor activity.
• Both telomerase and CAG promoters demonstrated comparable anti-tumor properties in vivo.