Tumours: Immunotherapy C Bryce Johnson, Medical University of South Carolina, Charleston, South Carolina, USA Mohamed L Salem, Tanta University, Tanta, Egypt Shikhar Mehrotra, Medical University of South Carolina, Charleston, South Carolina, USA David J Cole, Medical University of South Carolina, Charleston, South Carolina, USA Mark P Rubinstein, Medical University of South Carolina, Charleston, South Carolina, USA Based in part on the previous version of this eLS article ‘Tumours: Immunotherapy’ (2007) by Mohamed L Salem, Mark P Rubinstein and David J Cole. The mainstay of cancer treatment has historically involved therapies, such as surgery, chemotherapy or radiation, that were developed without regard for the patient’s immune system. However, as researchers have started to elucidate mechanisms by which the immune system can eradicate cancerous cells, an increasing num- ber of approaches have been developed that capitalise on an immune-based antitumour response. These therapies include nonspecific activation of the immune system using toll-like receptor ligands, cytokines or immune checkpoint inhibitors, or specific treatments, like mono- clonal antibody administration or vaccination, that dir- ectly target cancer cells. Perhaps, the most promising specific therapy is the adoptive transfer of genetically engineered tumour-reactive T cells, an approach that has already proven curative in some patients with meta- static disease. Cumulatively, these new immune-based approaches have great promise to revolutionise cancer therapy. In this article, we will outline the mechanisms and characteristics of these tumour immunotherapies, emphasising those with demonstrated clinical efficacy. Introduction The concept of modulating the immune system to achieve an antitumour response is not new, with numerous attempts documented throughout history. The first suc- cessful documented efforts at achieving an anticancer response via immunotherapy, however, were not achieved until the end of the nineteenth century when the surgeon William Coley noted the regression of an unresectable sarcoma subsequent to a postoperative wound infection. Building on this observation, he was able to show the objective regression of a variety of tumours using bacterial (Streptococcus) extracts (Coley’s toxins), presumably through a mechanism of nonspecific immune stimulation. Although Coley’s toxins treatment resulted in the encour- aging results of shrinking sarcoma, it came under a great deal of criticism because many doctors did not believe his results. Even though this criticism caused Coley’s toxins gradually to disappear from use, the modern science of cancer immunology revealed that Coley’s principles were correct and that many cancers are sensitive to an enhanced immune system. In fact, it is now well established that tumour growth is controlled by the immune system in a process called tumour immunoediting. This process has three major phases: elimination (tumour is eradicated), equilibrium (tumour is kept in check but not destroyed) and escape (tumour develops mechanisms to evade the immune system) (Schreiber et al., 2011). Restoring the immune system’s ability to destroy tumours is the goal of immunotherapies, and as we will highlight in this article, much progress has been made to achieve this goal. Particularly in the past few years, immunotherapies have been developed that achieve objective responses, and in some cases complete cures, against many cancers. These immunotherapies can be broadly divided into two cat- egories, nonspecific and specific immunotherapies. Non- specific therapies utilise agents that activate the immune system to overcome the tumour’s escape mechanisms. Once activated, the immune system can coordinate an anti- tumour response. Specific therapies involve direct targeting of tumour antigens, and it can be subdivided into two parts: (1) adoptive cell transfer (passive immunotherapy) and (2) vaccination (active immunotherapy) (Table 1). Adoptive transfer involves the direct transfer of the actual com- ponents of the immune system already capable of pro- ducing a specific immune response. These components could be in the form of cell-based or antibody-based therapies. In the case of cell-based adoptive therapy, pre- conditioning the patients with chemotherapeutic drugs or radiation is typically used to enhance the efficacy of this treatment regimen. Vaccination is defined as the adminis- tration of a particular antigenic element to induce a specific Advanced article Article Contents . Introduction . Nonspecific Immunotherapy . Specific Immunotherapy I: Adoptive Transfer . Specific Immunotherapy II: Vaccination . Conclusion Online posting date: 13 th June 2013 eLS subject area: Immunology How to cite: Johnson, C Bryce; Salem, Mohamed L; Mehrotra, Shikhar; Cole, David J; and Rubinstein, Mark P (June 2013) Tumours: Immunotherapy. In: eLS. John Wiley & Sons, Ltd: Chichester. DOI: 10.1002/9780470015902.a0001432.pub3 eLS & 2013, John Wiley & Sons, Ltd. www.els.net 1