
Preclinical studies
Studies on efficacy and mode of action
Preclinical study program of anticancer drug Mobilan (M-VM3) included studies aimed to select the optimal therapeutic area, confirm relevance of the drug mode of action in relation to the chosen therapeutic area, as well efficacy study on the animal model.
The selection of a tumor type for which adenovirus delivery system would be effective included several screening studies in which we managed to select tumors capable of transduction with adenovirus vector delivery system like Mobilan (M-VM3). The preliminary studies on selection of the therapeutic target allowed to detect that cells of most prostate tumors were CAR-positive and may be succesefully transduced by adenovirus system of gene delivery. Recent clinical results suggest that such transduction is happening clinical setting.
Anticancer activity of Mobilan (M-VM3) was examined on the model of spontaneous prostate tumor in mouse model TRAMP (transgene prostate adenocarcinoma in mice) and in CAR-positive syngene mouse model of breast cancer 4Т1. The first study demonstrated that Mobilan (M-VM3) directly administered to the ventral lobe of the prostate gland of TRAMP mice may suppress growth and development of spontaneous orthotropic cancer tumors. In mice with subcutaneously grown breast tumors 4Т1, single intratumor Mobilan (M-VM3) injection caused anticancer effect in comparison with control agents which was illustrated by slower mortality kinetics of animals and significant decrease of the mean tumor size to the end of observation period.
The specifically designed model cell systems in vitro showed activation of signaling pathway NF-kB with Mobilan.
As part of the work to confirm in vitro biological activity of the drug, the data were also obtained which showed that drug Mobilan (M-VM3) after its addition to eukaryotic cells recovered TLR5 expression in TLR5-negative cells (RAW-BLUE), as well induced dose-dependent expression of specific TLR5 ligand which was consistent with the declared mode of action.