Radioactive Microbes: Cancer Therapy Approaches

Abstract

With the majority of cancer patients succumbing to the metastatic form of the disease, there is an ongoing search for ways to block metastatic spread and render patients free from cancer. Radiovirotherapy involves the use of viruses to deliver radioisotopic treatment into infected cells, and several types of virus (e.g., measles virus, herpes simplex type 1 virus, adenovirus, and vaccinia virus), all of which possess oncolytic properties, have been utilized to deliver transgenes encoding for the human sodium iodide symporter (NIS). As the virus does not carry any radioactivity, radiovirotherapy is always a two-step strategy, with viral gene delivery followed by systemic administration of the radionuclide. The NIS transports 131I, which is used to treat thyroid diseases, and radiovirotherapy has been investigated using this radionuclide in experimental cancers, with encouraging results. In spite of some problems with viral delivery, radiovirotherapy has been consistently more efficient in treating experimental cancers than virotherapy alone. Yet another approach to radioactive microbe cancer therapy, radioactive bacteria (radiolisteria), employs a combinatorial agent capable of selectively infecting tumor cells and delivering a therapeutic radionuclide inside the tumor cells. The tumoricidal effect of such therapy results from the Listeria organisms killing tumor cells via the production of reactive oxygen species and a direct impact of radiation on cancer cells. Whilst the field of radioactive microbes for cancer therapy is still in its infancy, it is hoped that radioactive microbe therapy will be extended to clinical trials in the near future, hopefully with encouraging results. Keywords: radiovirotherapy; sodium iodide symporter (NIS); oncolytic virus/bacterium; 131iodine