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Cancer malignancies are responsible for approximately a quarter of all deaths in the developed world. Primary tumours can often be treated successfully with surgical resection, chemotherapy or radiation; however, these therapies are mostly ineffective against metastatic spreading. For this reason, the elimination or control of metastases is a primary goal for new cancer therapies. Immunotherapies harness the innate ability of the immune system to recognise and eliminate tumours. After decades of debate, it is now accepted that the immune system plays an important role in preventing tumours and can be stimulated to eradicate established tumours.
One of the first observations supporting the involvement of the immune system in the control of cancer is that immunocompromised individuals and animals have a higher rate of spontaneous tumours. More recently, it has been shown that immune cells collect at tumour sites and specifically respond to tumour-associated antigens (TAAs). Genetic instability and overexpression cause most tumours to express TAAs that offer new epitopes or aberrantly expressed self-epitopes that can be recognised by the immune system. Unfortunately, many cancers have developed mechanisms to subvert the immune system, including the loss of expression of TAAs or major histocompatibility complex (MHC) molecules, the production of immune-suppressing cytokines such as transforming growth factor β (TGFβ) and interleukin 10 (IL10), and/or the induction of regulatory/suppressor cells.
The primary goal of immunotherapy is to direct immune responses to tumours that either are ignored by the immune system or are actively suppressing the immune system. The first documented use of immunotherapy for cancer was over a hundred years ago, when a surgeon named William Coley injected attenuated bacteria (also known as Coley’s toxin) into tumours of sarcoma patients.1 With this treatment he achieved a cure rate of >10%. Coley’s toxin is a classic example of immune adjuvant therapy. Adjuvants typically …