Bacteriolytic Therapy

Abstract: When spores of the anaerobic bacterium Clostridium novyi-NT are systemically injected into animals, they germinate exclusively within the hypoxic regions of cancers. The germinated bacteria destroy adjacent tumor cells but spare a rim of well oxygenated tumor cells that subsequently expand. Surprisingly, we found that ≈30% of mice treated with such spores were cured of their cancers despite the viable tumor rim initially remaining after spore germination. The mechanism underlying this effect was shown to be immune-mediated, because cured animals rejected a subsequent challenge of the same tumor. Similar effects were observed in rabbits with intrahepatic tumors. It was particularly notable that the induced immune response, when combined with the bacteriolytic effects of C. novyi-NT, could eradicate large established tumors.

Abstract: This review deals with the role of microorganisms in spontaneous regression of a tumour. Spontaneous cancer regression is a phenomenon that has been described for many centuries. One of the most well known methods of inducing spontaneous regression of cancer is the application of Coley's toxin (heat-killed Streptococcus pyogenes and Serratia marcescens), which has been used for the successful treatment of sarcomas, carcinomas, lymphomas, myelomas and melanomas. In clinical practice, the use of Bacillus Calmette-Guerin vaccine for the treatment of superficial urinary bladder cancer is the most common instance of the application of microorganisms for the treatment of cancer. This review provides further information on other tested bacteria--Clostridium spp., Bifidobacterium spp., Lactobacillus spp. and Salmonella spp.--in this field of study. Among new age methods, bactofection, alternative gene therapy, combination bacteriolytic therapy and bacteria-directed enzyme prodrug therapy are some of the potential cancer treatment modalities that use microorganisms. We have also provided information about the interconnection among microorganisms, immune system response, and the possible mechanisms involved in the spontaneous regression of tumours.

Abstract: Hypoxia and anoxia are pathophysiologic characteristics of most solid tumors (1, 2). For nearly 150 years, nonpathogenic, anaerobic bacteria that preferentially localize and proliferate in the hypoxic regions of tumors have been investigated as treatments for experimental and human tumors with mixed success (Table 1). In recent years, there has been a renewed interest in using these bacteria as innovative delivery vehicles for gene therapy (Table 1). Now, as described in this issue of PNAS, Vogelstein and coworkers (11) have created a new strain of anaerobic bacteria, devoid of its toxic genes, that leads to dramatic and prolonged regression of subcutaneous tumors when systematically administered with conventional drugs. This strategy, referred to as combination bacteriolytic therapy (COBALT), adds a new weapon in the war against cancer. However, there are still obstacles that need to be overcome before it can be used safely in the clinic. Ironically, a tumor's metabolically compromised microenvironment provides a haven for a number of anaerobic bacteria.