Live bacteria as the basis for immunotherapies against cancer.

For more than a century, bacteria and bacterial products have been used for the treatment of cancer. Starting from the practical observation of tumor regression in individuals with concomitant bacterial infection, the field has evolved into some standard clinical practices, such as the use of BCG for the treatment of superficial bladder cancer. However, in the last few years, new applications have started to emerge that may profoundly change the perspective of the field. BCG can be engineered to express cytokines to improve its efficacy. Bacteria such as Salmonella and Listeria can be attenuated by genetically-defined mutations and provide effective vehicles for DNA vaccines encoding tumor-associated antigens. Salmonella and nonpathogenic strains of Clostridium can selectively accumulate in tumors in vivo, providing attractive delivery systems to target immunomodulatory molecules and therapeutic agents to the tumor site. Many of these new developments have been attempted for prophylactic or therapeutic vaccination in several different experimental models of cancer and in many cases, results from clinical trials are now emerging. There is still some way to go before achieving products that could be in routine use, but the field has great promise for the development of more effective immunotherapies for several different cancers. In this paper, we will review the current state of such applications and highlight some of the directions that the field may take.