Cancer Gene Therapy

Volume 465 of the series Advances in Experimental Medicine and Biology pp 57-63

Tumor-Targeted Salmonella

Highly Selective Delivery Vectors
  • David BermudesAffiliated withVion Pharmaceuticals, Inc.
  • , Brooks LowAffiliated withDepartment of Therapeutic Radiology, Yale University School of Medicine
  • , John PawelekAffiliated withDepartment of Therapeutic Dermatology, Yale University School of Medicine

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Genetically engineered Salmonella offer an intriguing new approach to selectively target solid tumors, including melanoma, lung, colon, breast, kidney and liver. These bacteria target tumors after systemic administration and selectively replicate within them. Specificity for tumors is often more than 1,000 times greater than for any other tissue. Auxotrophic mutations make these bacteria highly safe and form the basis for maintaining tumor specificity. An altered lipid greatly reduces the potential for septic shock yet also retains the antitumor properties of these bacteria. These bacteria have innate antitumor activity towards both primary and metastatic tumors and the ability to deliver proteins capable of activating chemotherapeutic agents directly within tumors. The delay in tumor growth results in mice that survive up to twice as long. These bacteria are susceptible to a wide range of antibiotics, allowing external control of the vector after administration. The combination of these features within a single vector seems especially surprising considering their unlikely source.