Tumour-SelectiveSalmonella-BasedCancer Therapy

Cancer therapies fail for several primary reasons; lack of drug effect on the cancerous, lack of selectivity for the cancerous tissue, and/or inadequate delivery to the tissue. Drug effect and selectivity can be improved by increased understanding molecular and cellular differences between cancer and normal tissues, thus the design of drugs that potently affect cancer-specific molecular targets with malignant behaviour. Another approach is to improve the selective of anti-cancer agents to tumours. One approach is to use carriers that bind to-specific targets, such as antibodies (Hall, 1995). However, most targeting, even if selective, tend not to deliver sufficiently high concentrations of agent to the tumour to induce significant therapeutic effects. Recent findings that the pathogenic bacterium Salmonella, when genetically modified, can be to selectively deliver therapeutic agents to solid tumours at high concentrations(Pawelek et al., 1997; Low et al., 1999a). These attenuated bacteria are administered systemically or locally, whereupon they typically replicate I 000 times greater the tumour than in other tissue. The basis for preferential colonization and of Salmonella in tumours appears to include some of the same characteristics tumours that provide resistance to drug and immune-based therapies(Bermudes et al., 2000a,b).