Therapeutic properties of a vector carrying the HSV thymidine kinase and GM-CSF genes and delivered as a complex with a cationic copolymer

• DOI: 10.1186/s12967-015-0433-0
• Publication Date: 2015-03-02T22:57:23Z
• Authors: Irina V Alekseenko; Eugene V Snezhkov; Igor P Chernov; Victor V Pleshkan; Victor K Potapov; Alexander V Sass; Galina S Monastyr...; Eugene P Kopantzev; Tatyana V Vinogra...; Yuri V Khramtsov; Alexey V Ulasov; Andrey A Rosenkranz; Alexander S Sobolev; Olga A Bezborodova; Anna D Plyutinskaya; Elena R Nemtsova; Raisa I Yakubovskaya; Eugene D Sverdlov
• Keywords: Suicide gene; Thymidine kinase

Gene-directed enzyme prodrug therapy (GDEPT) represents a technology to improve drug selectivity for cancer cells. It consists of delivery into tumor cells suicide gene responsible in situ conversion cytotoxic metabolites. Major limitations GDEPT that hinder its clinical application include inefficient and poor activation by enzymes. We tried overcome these constraints through combination with immunomodulating therapy. Viral vectors dominate present-day trials due efficient transfection production therapeutic genes. However, safety concerns associated severe immune inflammatory responses as well high cost the viruses can limit use virus-based therapeutics. this problem using simple nonviral system. studied antitumor efficacy PEI (polyethylenimine)-PEG (polyethylene glycol) copolymer carrying HSVtk combined one vector granulocyte–macrophage colony-stimulating factor (GM-CSF) cDNA. The system HSVtk-GM-CSF/PEI-PEG was tested vitro various mouse human cell lines, ex vivo models. showed effectively inhibited growth transplanted tumors, suppressed metastasis increased animal lifespan. demonstrated appreciable shrinkage inhibition could be achieved low toxic chemical carrier – PEI-PEG copolymer. Our data indicate cytokine may provide powerful approach treatment solid tumors their metastases.