ABSTRACT
As strict anaerobic bacteria, clostridia can be exploited for the treatment of cancer. This is because, upon spore administration to tumor-bearing organisms, Clostridium specifically colonizes the hypoxic/necrotic region of solid tumors, which is highly resistant to radioand chemotherapy and, hence, with a negative outcome for tumor control. In this respect, recombinant clostridia expressing and eventually secreting therapeutic proteins within the tumor microenvironment have potential in tumor treatment, as they can transfer proteins of therapeutic interest to a critical region of the tumor. The delivery of therapeutic proteins to the hypoxic/necrotic region of the tumor may, therefore, allow its control from inside. Moreover, the Clostridium-mediated protein transfer provides several advantages compared to the classical gene therapy for cancer. Tumor cells do not need to be genetically modified, evading possible cancerogenic events caused, for instance, by random insertion of foreign DNA into the genome. In addition, the bacterial transfer system can be regarded as safe, since targeted gene expression can be stopped at any time by elimination of the tumorcolonizing bacteria through administration of suitable antibiotics. In combination with the conventional tumor treatment modalities like radioand chemotherapy, it may lead to the increase of the therapeutic ratio of cancer.
