Aerosolized BC-819 inhibits primary but not secondary lung cancer growth.

Despite numerous efforts, drug based treatments for patients
suffering from lung cancer remains poor. As a promising
alternative, we investigated the therapeutic potential of BC-819
for the treatment of lung cancer in mouse tumor models. BC-819 is a
novel plasmid DNA which encodes for the A-fragment of Diphtheria
toxin and has previously been shown to successfully inhibit tumor
growth in human clinical study of bladder carcinoma. In a first set
of experiments, we examined in vitro efficacy of BC-819 in human
lung cancer cell-lines NCI-H460, NCI-H358 and A549, which revealed
>90% reduction of cell growth. In vivo efficacy was examined in
an orthotopic mouse xenograft lung cancer model and in a lung
metastasis model using luminescent A549-C8-luc adenocarcinoma
cells. These cells resulted in peri- and intra-bronchiolar tumors
upon intrabronchial application and parenchymal tumors upon
intravenous injection, respectively. Mice suffering from these lung
tumors were treated with BC-819, complexed to branched
polyethylenimine (PEI) and aerosolized to the mice once per week
for a period of 10 weeks. Using this regimen, growth of
intrabronchially induced lung tumors was significantly inhibited
(p = 0.01), whereas no effect could be observed in mice suffering
from lung metastasis. In summary, we suggest that aerosolized
PEI/BC-819 is capable of reducing growth only in tumors arising
from the luminal part of the airways and are therefore directly
accessible for inhaled BC-819.