Figure 2. The transport properties of bacterial therapies produce preferable drug concentration profiles.

When injected systemically, bacteria (red syringe, green organisms), specifically accumulate in tumors and migrate to distal regions far from vasculature (brown cells). These distal regions are typically hypoxic and hypoglycemic and contain quiescent and necrotic cells. Once triggered (small red arrows), bacteria begin to produce therapeutic molecules (red ovoids) that diffuse (large red arrows) into viable tissue (clear cells). Systemically injected (small blue arrows), passive chemotherapeutic molecules (blue cubes) diffuse into tumor tissue from blood vessels (large blue arrows). The concentration of bacterially produced molecules (red lines) is greatest in distal tumor regions and would remain constant as long as expression of these proteins continues. The concentration of chemotherapeutic molecules is greatest in systemic blood and drops as it is cleared by the liver or kidneys. Based on these profiles, bacterially produced molecules will be more cytotoxic (dotted line) in the distal regions of tumors and less systemically toxic. The profile of passive molecules is less favorable, with more systemic toxicity and less efficacy deep in tissue.