Figure 3.

Delivery of Cancer Terminator Viruses (CTVs) systemically following complexing with microbubbles (MB) coupled with ultrasound-targeted MB destruction, the UTMD approach. Complexes of CTVs with MBs are delivered intravenously (Box A, Ad incorporated in the lipid shell of MBs), which are released at the primary tumor site by the application of ultrasound (Box B, sonoporation of MBs in the tumor with an ultrasound probe). After intracellular entry, the CTVs replicate selectively in tumor cells, resulting in robust production of mda-7/IL-24 that when translated into MDA-7/IL-24 protein cause ER stress and “unfolded protein stress response” and cancer cell death. MDA-7/IL-24 is subsequently released into the circulatory system and due to virtue of its “bystander activity” (Box C, binding of MDA-7/IL-24 with IL-20R1/IL-20R2 or IL-20R1/IL-22R1 and promoting intracellular signaling leading to autocrine production of MDA-7/IL-24), which would be anticipated to induce tumor-specific apoptosis of primary and distant tumors, antiangiogenic effects in primary and distant tumor vasculatures, and immune modulatory effects targeting tumors for immune destruction. It is believed to be the “summation” of these multifaceted antitumor properties of MDA-7/IL-24 that promotes selective destruction of both primary and distant tumors. (Adapted from Das et al., Adv. Cancer Res., 2012).