Tumor-targeting prodrug-activating bacteria for cancer therapy

Increasing the specificity of chemotherapy may improve the efficacy of cancer treatment. Toward this aim, we developed a strain of bacteria to express enzymes for selective prodrug activation and non-invasive imaging in tumors. β-glucuronidase and the luxCDABE gene cluster were expressed in the DH5α strain of Escherichia coli to generate DH5α-lux/βG. These bacteria emitted light for imaging and hydrolyzed the glucuronide prodrug 9ACG to the topoisomerase I inhibitor 9-aminocamptothecin (9AC). By optical imaging, colony-forming units (CFUs) and staining for βG activity, we found that DH5α-lux/βG preferentially localized and replicated within CL1-5 human lung tumors in mice. The intensity of luminescence, CFU and βG activity increased with time, indicating bacterial replication occurred in tumors. In comparison with DH5α-lux/βG, 9AC or 9ACG treatment, combined systemic administration of DH5α-lux/βG followed by 9ACG prodrug treatment significantly (P<0.005) delayed the growth of CL1-5 tumors. Our results demonstrate that prodrug-activating bacteria may be useful for selective cancer chemotherapy.