One of the main objectives of
cancer therapy is to enhance the effectiveness of the
drug by concentrating it at the target site and to minimize the undesired side effects to nontarget cells. We have previously constructed a fusion
protein, Lodavin, consisting of
avidin and the endocytotic part of the
low-density lipoprotein receptor, and demonstrated its applicability to transient drug targeting in vivo. In this study we produced a lentiviral vector expressing this fusion
protein and evaluated its safety and efficacy. The results showed that lentivirus-mediated gene transfer led to long-term
avidin fusion
protein expression on
glioma cells and that the receptor was able to bind biotinylated compounds. Repeated administration was proven feasible and the optimal time frame(s) for administration of biotinylated therapeutic and/or imaging compounds was elucidated. Intravenous or intracranial injection of the virus into BDIX rats led to the production of
antibodies against transgene (
avidin), but repeated administration of the vector was unable to boost this effect.
Neutralizing antibodies against the lentivirus were also detected. Furthermore, we showed that the anti-
avidin antibodies did not significantly affect the
ligand-binding capacity of the
avidin fusion
protein. The therapeutic efficacy of
avidin fusion
protein in
tumor treatment was tested in vitro with biotinylated and nonbiotinylated nanoparticles loaded with
paclitaxel. In vivo applicability of lentivirus was studied in the BDIX rat
glioma model, in which high receptor expression was detected in the
tumor area. The lentivirus-mediated delivery of the
avidin fusion
protein thus represents a potential approach for the repeated targeting of cytotoxic compounds to
cancer cells.