Genetically engineered E. coli as a protein delivery vehicle for killing cancer cells

Extract: The beneficial effects of bacteria on rejection of and resistance to tumors have been observed since the 18th century. Physicians have recorded hundreds of cases of spontaneous regression of many types of cancer following bacterial infections, such as staphylococcal or mixed infections, or bacterial vaccines. For example, significantly lower recurrence and number of metastases were recorded in sarcoma patients with concurrent streptococcal infection occurring either spontaneously or by inoculation. More recently, a decreased incidence of malignancy has been recorded in areas or subsets of populations where infectious diseases are endemic. For example, a Swiss study of hospitalized patients over a 20 year period recorded that the previous incidence of acute infections and acute inflammatory episodes was almost nil in groups of cancer patients, compared with a much higher incidence in the non-cancerous groups. Studies in the 1960s with Clostridium showed that this anaerobic bacterium could selectively target and grow inside experimental tumors in mice, leading to tumor regression. However, clinical trials with Clostridium had to be abandoned due to severe toxicities. In the last few years interest in using bacteria as cancer therapies has been reignited. Advances in genetic engineering have enabled modifications of bacteria to reduce toxicity, however, clinical trials with attenuated bacteria such as Salmonella have failed to provide therapeutic benefits that outweigh toxicities in cancer patients.