Use of preferentially replicating bacteria for the treatment of cancer.

Abstract

The past several years have seen renewed interest in the treatment of cancer with live microorganisms, based on the observation that some microorganisms display selective replication or preferential accumulation in the tumor microenvironment. Preferential replication offers great potential to amplify the therapeutic effect of the microorganism while sparing normal tissues from toxicity. Much of the current research intended to achieve selective replication within, and lysis of, tumor cells has focused on viruses, but recent observations in murine models with facultative anaerobic bacteria (1), as well as data generated more than 30 years ago with obligate anaerobic bacteria (2), indicate that some bacterial species can also preferentially replicate and accumulate within tumors. In contrast to viruses, the bacteria reside primarily in the extracellular tumor microenvironment (3) and possess certain features that may be advantageous in the treatment of cancer. Thus, bacteria are motile, which facilitates their spread throughout the tumor and can help target systemic disease. Because of their large genome size, bacteria can readily express multiple therapeutic transgenes, such as cytokines or pro–drug-converting enzymes, and their spread can be controlled with antibiotics if necessary.