Prolonged in vivo expression and anti-tumor response of DNA-based anti-HER2 antibodies.

ABSTRACT: Antibody gene transfer presents an appealing alternative to conventional antibody protein therapy. This pre-clinical study evaluates the impact of various parameters on the pharmacokinetics and efficacy of in vivo expressed DNA-based anti-HER2 monoclonal antibodies (mAbs), newly engineered and delivered via intramuscular electrotransfer in mice. Plasma concentrations of trastuzumab and 4D5, its murine IgG1 equivalent, peaked on average between 1-15 µg/ml, depending on the administration and configuration of the encoding plasmid DNA (pDNA). A dual expression cassette system outperformed a single 2A-based cassette, and the CAG promoter was superior to a muscle-specific ΔUSE-based promoter. A 'gene therapy-compatible' Gene Transport Unit (gtGTU, FIT Biotech), a plasmid backbone that co

SUBMITTER: Hollevoet K 

PROVIDER: S-EPMC5862603 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature