Designer bacteria as anti-cancer agents

Abstract

To date, cancer persists as one of the most devastating diseases worldwide. Problems such as inoperable primary tumours due to late stage diagnosis, presence of metastatic tumours, and tumour resistance to chemotherapy and radiotherapy have remarkably limited the therapeutic effects of existing treatments. To address these problems, cancer gene therapy has been under rapid development over the past two decades, which is specifically designed to deliver therapeutic genes to treat cancers using vector systems. However, the lack of an ideal vector has been a major drawback. Recent understanding of hypoxic and necrotic regions within solid malignancies and rapid development of recombinant DNA technology have reignited the idea of using anaerobic bacteria such as Clostridium as novel intra-tumoural delivery systems for anti-cancer therapeutics. These bacterial vectors have unique advantages over other delivery systems and are likely to become the vector of choice for cancer therapy in the near future. At present, Clostridium-mediated cancer therapy has shown some promising therapeutic efficacy against a number of solid malignancies, providing an opportunity for the development of novel anti-cancer gene therapies. In the last decade, targeted cancer therapy has witnessed its most impressive progress. Anti-cancer monoclonal antibodies (mAb) and recombinant immunotoxins against specific tumour cell surface antigens such as epidermal growth factor receptor (EGFR) have shown encouraging therapeutic efficacy against a large spectrum of cancers. However, difficulties such as insufficient intra-tumoural drug delivery have been preventing the therapy from reaching its full therapeutic potentials.