Therapeutic live vaccines as a potential anticancer strategy

Abstract

The design of efficient cancer treatments is one of the major challenges of medical science. Therapeutic vaccines of cancer have been emerged as an attractive approach for their capacity of breaking the immune tolerance and invoking long-term immune response targeting cancer cells without autoimmunity. An efficient antigen delivery system is the key issue of developing an effective cancer vaccine. In this regard, live vaccination strategies including various live bacterial and viral vectors have attracted a great attention. Several bacterial strains such as Salmonella, Listeria monocytogenes and Lactococcus lactis effectively colonize solid tumors and act as antitumor therapeutics. On the other hand, the use of viruses as vaccine vectors such as Vaccinia, Adenovirus, Herpes simplex virus, Paramyxovirus and Retroviruses utilizes mechanisms that evolved in these microbes for entering cells and capturing the cellular machinery to express viral proteins. Viral/bacterial-vectored vaccines induce systemic T-cell responses including polyfunctional cytokine-secreting CD4+ and CD8+ T-cells. However, there is an urgent need for the development of new safe live vaccine vectors that are capable of enhancing antigen presentation and eliciting potent immune responses without the risk of development of disease in humans. Recently, nonpathogenic parasites including Leishmania tarentolae, Toxoplasma gondii and Trypanosoma cruzi have emerged to be a novel candidate for gene delivery and heterologous genes expression. In this review, recent researches on cancer therapy using genetically modified bacteria and virus are summarized. In addition, live parasite-based vectors will be discussed as a novel anticancer therapeutic approach.